Boron complexation strategy for use in manipulating 1-acyldipyrromethanes

ABSTRACT

A method of making a metal complex comprises combining a 1-monoacyldipyrromethane with a compound of the formula R 1 R 2 MX, wherein M is boron, R 1  and R 2  are each independently organic substituents; and X is an anion leaving group; to produce a metal complex of the formula DMR 1 R 2  wherein DH is a 1-monoacyldipyrromethane. The methods and complexes are useful for the purification and synthesis of dipyrromethanes and porphyrins.

This invention was made with Government support under grant numberGM36238 from the National Institutes of Health. The United Statesgovernment has certain rights to this invention.

RELATED APPLICATIONS

This application is related to U.S. patent application Ser. No.10/164,181, filed Sep. 3, 2003, titled Facile Synthesis of1,9-Diacyldipyrromethanes; and

Ser. No. 10/698,255, filed Oct. 31, 2003, titled Synthesis ofPhosphono-substituted Porphyrin Compunds for Attachment to Metal OxideSurfaces,

the disclosures of which are incorporated by reference herein in theirentirety.

FIELD OF THE INVENTION

This invention concerns methods and intermediates useful for thesynthesis of 1-acyldipyrromethanes, along with methods of use thereof.

BACKGROUND OF THE INVENTION

Rational syntheses of a variety of porphyrinic compounds bearing diversepatterns of meso substituents have been developed recently. Theporphyrinic compounds include porphyrins,¹⁻³ chlorins,⁴ corroles,⁵ andbilanes.⁶ The syntheses begin with dipyrromethanes (1), and, dependingon desired substitution pattern, also employ 1-acyldipyrromethanes (2)and 1,9-diacyldipyrromethanes (3) (Chart 1).^(1,2) 1-Acyldipyrromethanesare readily prepared from the corresponding dipyrromethane, while1,9-diacyldipyrromethanes can be prepared by 9-acylation of a1-acyldipyrromethane or by 1,9-diacylation of a dipyrromethane. Althoughthe acylation procedures work reasonably well, purification is difficultowing to the lack of crystallinity of the acyldipyrromethanes.Accordingly, the mixture containing the acyldipyrromethane is usuallyseparated by chromatography, which can be tedious owing to the tendencyof the acyldipyrromethanes to streak on chromatographic media.

One of our objectives over the past few years has been to increase thescale of porphyrin syntheses, which entails decreasing if noteliminating reliance on chromatography for purification. Toward thisgoal, we recently developed a simple procedure for isolating a1,9-diacyldipyrromethane from the diacylation reaction mixture byforming a dialkyltin complex (Chart 2).⁷ Dipyrromethanes,1-acyldipyrromethanes or 1,8-diacyldipyrromethanes did not give tincomplexes. The tin complex of a 1,9-diacyldipyrromethane was hydrophobicand crystalline, greatly facilitating isolation. In addition, the tincomplex readily underwent decomplexation upon treatment with dilutetrifluoroacetic acid. The availability of the tin-complexation procedurehas enabled routine synthesis of multigram quantities of1,9-diacyldipyrromethanes.

SUMMARY OF THE INVENTION

We herein describe the development of a boron-complexation strategy forthe isolation and purification of 1-acyldipyrromethanes formed uponacylation of dipyrromethanes. We also describe use of the1-acyldipyrromethane-boron complexes in porphyrin-forming reactionsfollowing similar procedures employed with 1-acyldipyrromethanes. Theability to complex the 1-acyldipyrromethane greatly facilitatespurification and enables synthesis of 1-acyldipyrromethanes at themultigram scale.

Thus, a first aspect of the present invention is a method of making ametal complex, comprising: (a) providing a 1-monoacyldipyrromethane; andthen (b) combining (e.g., in a suitable solvent such as dichloromethane)said 1-monoacyldipyrromethane with a compound of the formula R¹R²MX,wherein M is boron, R¹ and R² are each independently organicsubstituents (preferably substituents in which M is coupled by covalentlink to a carbon atom in the organic substituents); and X is an anionleaving group; to produce a metal complex of the formula DMR¹R² whereinDH is said 1-monoacyldipyrromethane.

A further aspect of the present invention is a1-monoacyldipyrromethane-boron complex of the formula DMR¹R², wherein:DH is a 1-monoacyldipyrromethane, M is boron, and R¹ and R² are asdescribed above, and in further detail below. The complex may beprovided in solid form, including crystal solid form.

A further aspect of the present invention is a method of making aporphyrin, comprising: providing a 1-monoacyldipyrromethane-boroncomplex as described herein, and then reducing said1-monoacyldipyrromethane in said complex without prior decomplexation ofsaid boron to produce said porphyrin.

A further aspect of the present invention is a method of making a1,9-diacyldipyrromethane metal complex, comprising: providing a1-monoacyldipyrromethane-boron complex as described herein; and thenacylating said 1-monoacyldipyrromethane in said complex at the 9position with a pyridyl thioate Mukaiyama reagent in the presence of aGrignard reagent and a base to produce said 1,9-diacyldipyrromethanemetal complex.

A further aspect of the present invention is a method of making acompound useful as a chlorin eastern half, comprising: providing a1-monoacyldipyrromethane-boron complex as described above, and thenhalogenating (e.g., brominating) said 1-monoacyldipyrromethane in saidcomplex at the 9 position to produce a 1-acyl-9-halodipyrromethane-boroncomplex useful as a chlorin eastern half.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows an ORTEP drawing of the X-ray structure of a1-acyldipyrromethane-boron complex of the present invention (compound6a-BBN). The diethyl ether solvate molecule is also illustrated. Allellipsoids are contoured at the 50% level, and hydrogens are omitted forclarity.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

The present invention is explained in greater detail below. Thisdescription is not intended to be a detailed catalog of all thedifferent ways in which the invention may be implemented, or all thefeatures that may be added to the instant invention. For example,features illustrated with respect to one embodiment may be incorporatedinto other embodiments, and features illustrated with respect to aparticular embodiment may be deleted from that embodiment. In addition.numerous variations and additions to the various embodiments suggestedherein will be apparent to those skilled in the art in light of theinstant disclosure which do not depart from the instant invention.Hence, the following specification is intended to illustrate someparticular embodiments of the invention, and not to exhaustively specifyall permutations, combinations and variations thereof.

“Alkyl,” as used herein, refers to a straight or branched chainhydrocarbon containing from 1 to 10 or 20 carbon atoms, or more.Representative examples of alkyl include, but are not limited to,methyl, ethyl, n-propyl, iso-propyl, n-butyl. sec-butyl, iso-butyl,tert-butyl, n-pentyl, isopentyl, neopentyl, n-hexyl, 3-methylhexyl,2,2-dimethylpentyl, 2,3-dimethylpentyl, n-heptyl, n-octyl, n-nonyl,n-decyl, and the like, which may be substituted or unsubstituted.

“Aryl,” as used herein, refers to a monocyclic carbocyclic ring systemor a bicyclic carbocyclic fused ring system having one or more aromaticrings. Representative examples of aryl include pyridyl, azulenyl,indanyl, indenyl, naphthyl, phenyl, tetrahydronaphthyl, and the like,which may in turn be substituted or unsubstituted.

“Acyl” is intended to mean a —C(O)—R group, where R is a suitablesubstituent such as H, alkyl or aryl, which may in turn be substitutedor unsubstituted.

“Dipyrromethane” as used herein includes an unsubstituted or substituteddipyrromethane, which may be substituted one or more times at the 1, 2,3, 5, 7, 8 or 9 positions with any suitable substituent such as halo,carbonyl, alkyl, fluoroalkyl including perfluoroalkyl, aryl (e.g., arylat the 5 position; alkyl at the 1 and/or 9 position), fluoroarylincluding perfluoroaryl, etc. Dipyrromethanes may be coupled toporphyrinic macrocycles at any suitable position on the dipyrromethanes,including the 1, 2, 3, 5, 7, 8, or 9 position.

“Hindered alkyl amine base” as used herein refers to an amine basecontaining bulky substituents, such as in triethylamine.diisopropylethylamine, and triphenylamine, and not as in propyl amine.

“Halo” as used herein refers to chloro, fluoro, bromo, or iodo.

“Active Ester” as used herein refers to a compound which may be used toacylate a dipyrromethane or 1-acyldipyrromethane. In general an activeester is a compound of the general formula RCOX, where X is a leavinggroup. Any suitable leaving group may be used, including but not limitedto alkylthio, arylthio, acyloxy (i.e., (RCO)₂O), 2,4-dinitrophenyloxy,etc.

“Vilsmeier reagent” as used herein refers to a composition comprised ofa dialkylamide and POCl₃. The dialkylamide may be of the general formulaRC(═O)NR′R′, where R is H, alkyl or aryl, and R′ is alkyl, an example ofsuch a dialkylamide being N-acylmorpholide.

“Anion leaving group” as used herein may be any suitable anionic leavinggroup, including but not limited to Cl, Br, and OTF (or “triflate”,O₃SCF₃).

“Grignard reagent” has its conventional meaning in the art and includescompounds of the general formula RMgX, where X is bromo, chloro, oriodo, preferably bromo, and R is alkyl or aryl, preferably ethyl,sec-butyl, or mesityl.

“Hindered Grignard reagent” refers to a Grignard reagent as describedabove in which R is a bulky group such as mesityl, or more generally agroup of the formula:

wherein R¹, R² and R³ are each independently selected C1–C4 alkyl.

“Mukaiyama reagent” is described in further detail below.

“Eastern half” and “Western half” are as described in further detailbelow.

“Disilazane” as used herein refers to compounds of the formula:

wherein R¹ through R⁶ are each independently selected from the groupconsisting of alkyl (e.g., methyl, ethyl, propyl) and aryl (e.g.,phenyl).

All United States patent references cited herein are to be incorporatedby reference herein in their entirety.

Starting material 1-monoacyldipyrromethanes. Starting materials for themethods described herein are generally prepared by acylating adipyrromethane. As such the starting materials are typically provide ina crude form or mixture combined with other reaction reagents andproducts. Depending upon the end use planned for the product, thedipyrromethane may be substituted at the 5 position with H, alkyl, oraryl; or in other embodiments may be substituted at the 5 position witha substituent such as a dipyrromethane, porphyrin, dipyrrin, ordiacyldipyrromethane (which substituent may be directly coupled at the 5position or coupled by an intermediate linking group such as an alkyl oraryl group). Acylation of the dipyrromethane may be carried out in anyof a variety of ways. In one embodiment, acylating carried out byreacting the dipyrromethane with a compound of the formula RCOX, where Ris an organic substituent such as alkyl or aryl and X is halo, to form amixed reaction product comprising a 1-monoacyldipyrromethane acylated atthe 1 position with RCO—. In another embodiment, acylating is carriedout by reacting the dipyrromethane with an acid chloride and a Grignardreagent to form the mixed reaction product comprising a1-monoacyldipyrromethane. In another embodiment, acylating is carriedout by reacting the dipyrromethane with an active ester to form themixed reaction product comprising a 1-monoacyldipyrromethane. In anotherembodiment, acylating is carried out by reacting the dipyrromethane witha Vilsmeier reagent to form a mixed reaction product comprising a1-monoacyldipyrromethane. See. e.g., D. Gryko et al., J. PorphyrinsPhthalocyanines 7, 239–248 (2003).

Making 1-monoacyldipyrromethae metal complexes and separation of suchcomplexes. As noted above, the present invention provides a method ofmaking a metal complex, comprising: (a) providing a1-monoacyldipyrromethane and then (b) combining (e.g., in a suitablesolvent such as dichloromethane) said 1-monoacyldipyrromethane with acompound of the formula R¹R²MX, wherein M is boron, R¹ and R² are eachindependently organic substituents (preferably substituents in which Mis coupled by covalent link to a carbon atom in the organicsubstituents); and X is an anion leaving group; to produce a metalcomplex of the formula DMR¹R², wherein DH is said1-monoacyldipyrromethane. Illustrative organic substituents for R¹ andR² are alkyl, alkenyl, alkynyl, and aryl, each of which can beunsubstituted or substituted one or more times with a substituentselected from the group consisting of alkyl, alkenyl, alkynyl, aryl,alkoxy, alkylcarbonyl, alkylcarbonyloxy, alkylsulfinyl, alkylsulfonyl,alkylthio, halo, cyano, nitro, sulfo, oxo, formyl, azido, and carbamoyl.

In some embodiments of the foregoing, the combining step is carried outby combining a mixture such as a crude reaction mixture containing the1-monoacyldipyrromethane as a reaction product, along with otherundesired compounds, with the compound of the formula R¹R²MX. Forexample, the combining step may he carried out in a solution and saidmetal complex is solubilized or suspended in said solution, said methodfurther comprising the steps of: (c) combining said metal complex with ahindered alkyl amine base in an organic solvent to form a solid (e.g., acrystal solid) comprising said metal complex; and then (d) separatingthe complex from the organic solvent by filtration, centrifugation,sedimentation, or any other suitable separation technique. The time andtemperature of the combining step is not critical, but may for examplebe from 1 or 2 minutes to 24 hours in duration, and is most convenientlycarried out for 10 minutes to two hours, at a temperature range of −20°C. to 50 or 100° C. or more (e.g., room temperature). Any suitableorganic solvent may be used, including but not limited to methylenechloride, chloroform, 1,2-dichloroethane, toluene, chlorobenzene, etc.

In some embodiments the method further comprises the step of: (c)decomplexing said 1-monoacyldipyrromethane from said metal complex bycombining the metal complex with an hydroxide, an alcohol, water, orcombination thereof. Typical sources of hydroxide include but are notlimited to KOH, NaOH, LiOH, Ba(OH)₂, Mg(OH)₂, etc. Typical alcoholsinclude but are not limited to methanol, neopentyl glycol, ethanolamine,polyethylene glycol, 1,3-propanediol, pentaerythritol, and polyvinylalchol. Smooth decomplexation is obtained in refluxing solvents composedof water and tetrahydrofuran or alcohol and tetrahydrofuran.Decomplexation can be carried out in solution or with the hydroxy groupthat is coupled to (e.g., covalently coupled to) a solid support such asa solid support in accordance with known techniques.

In some embodiments, the compound of formula R¹R²MX may be immobilizedon a such as a polymer support, where the groups R constitute a portionof the polymer or are otherwise coupled to the polymer (withimmobilization on the solid support facilitating the subsequentseparation of the acylated dipyrromethane product). Hence the methodfurther comprises the step of: (c) releasing said1-monoacyldipyrromethane complex from said solid support, whichreleasing may be carried out utilizing the decomplexing proceduresdescribed above.

Thus the present invention provides a 1-monoacyldipyrromethane-boroncomplex of the formula DMR¹R², wherein: DH is a1-monoacyldipyrromethane, M is boron, and R¹ and R² are as describedherein. The complex may be provided in solid form, including crystalsolid form.

Direct synthesis of porphyrins. Among other things the present inventionprovides a method of making a porphyrin, comprising: providing a1-monoacyldipyrromethane-boron complex as described herein, and thenreducing said 1-monoacyldipyrromethane in the complex without priordecomplexation of said boron to produce said porphyrin. In someembodiments the reducing step is carried out with NaBH₄ in an organicsolvent.

Making 1,9-diacyldipyrromethanes and porphyrins therefrom. A furtheraspect of the present invention is a method of making a1,9-diacyldipyrromethane metal complex, comprising: providing a1-monoacyldipyrromethane-boron complex as described herein; and thenacylating said 1-monoacyldipyrromethane in said complex at the 9position with a pyridyl thioate Mukaiyama reagent in the presence of aGrignard reagent and a base to produce said 1,9-diacyldipyrromethanemetal complex. Preferably the conjugate acid of said base has a pK_(a)greater than that of the conjugate acid of the nonacylated pyrrole groupin said 1-monoacyldipyrromethane; thus the conjugate acid of the basetypically has a pK_(a) greater than 17. When the base is formed in situ(in which case at least a second equivalent of the Grignard reagent istypically required), the conjugate acid of the base preferably has apK_(a) less than that of the conjugate acid of the Grignard reagent (forexample, a pK_(a) less than 45). When the base is preformed and notformed in situ the pK_(a) of the conjugate acid thereof may be greater,e.g., 50 or 60. The base may be the deprotonated form of atetraalkylpiperidine (where said alkyl may be C1 to C4 alkyl, such astetramethylpiperidine), dicycloalkylamine (where said alkyl may be C4 toC8 alkyl, such as dicyclohexylamine), or disilazane (as describedabove), accompanied by a cation such as K⁺, Na⁺, Rb⁺, Cs⁺, Ca²⁺, Be²⁺,Zn²⁺, Al³⁺, etc., preferably Li⁺ and Mg²⁺, most preferably Mg²⁺.Preferred bases are compounds of the formula XMZ, where X is adisilazane as described above in deprotonated form, M is a cation asdescribed above, and Z if present is alkyl, halo, or other anion forcharge balance. Suitable Grignard reagents are known in the art, aredescribed above, and are also described in, among other references, U.S.Pat. Nos. 6,617,282, 6,608,212, 6,603,000 and 6,600,040. The Mukaiyamareagent is, in general, any suitable Mukaiyama reagent, typically a2-S-pyridyl thioate. The reaction may be carried out in any suitable(preferably non-aqueous) organic solvent, such as an ethereal solventsuch as tetrahydrofuran (THF). at a temperature of from −78° C. to 100°C. and any suitable pressure, and is preferably carried out at roomtemperature under ambient pressure.

Where no base is used for 9 acylation and 2 equivalents of ethylmagnesium bromide (Grignard reagent) is used (in which case oneequivalent of the Grignard reagent serves as the base), the results arenot so good. However, if two equivalents of a hindered Grignard reagent,such as mesityl-MgBr, are used, the 9-acylation results are excellent,regardless of whether a base such as a disilazane base is present.Evidently, mesityl-MgBr is a more hindered base than that formed with adisilazane, and provides even better results than the disilazane.

1,9-diacyldipyrromethanes produced in metal complexes as described abovemay in turn be reduced, while still within the metal complex, with areducing agent (e.g. NaBH₄) to form a diol from the1,9-diacyldipyrromethane in the complex, and the diol then condensingwith a dipyrromethane in accordance with known techniques to form aporphyrin ring compound therefrom.

In some embodiments of the foregoing, the method further comprises thestep of decomplexing the 1,9-diacyldipyrromethane from said metalcomplex by combining the metal complex with an hydroxide, an alcohol,water, or combination thereof in essentially the same manner asdescribed above.

In some embodiments, the present invention further provides a method ofmaking a metal complex (typically to aid in purifying the1,9-diacyldipyrromethanes), comprising: reacting a1,9-diacyldipyrromethane with a compound of the formula R¹R²M′X′₂ in thepresence of a base, where R¹ and R² are the same as given above, M′ isSn, Si, Ge or Pb (preferably Sn), and X′ is halo (e.g., chloro, bromo,iodo), OAc (where OAc is acetate), acac (acetylacetonate) or OTf (whereOTf is triflate), to form a metal complex of the general formulaDM′R¹R², wherein DH₂ is the 1,9-diacyldipyrromethane. Suitable basesinclude but are not limited to triethylamine, tributylamine,N,N-diisopropylamine, 1,8-diazabicyclo[5.4.0]undec-7-ene (or “DBU”),1,5-diazabicyclo[4.3.0]non-5-ene (or “DBN”), and2,6,-di-tert-butylpyridine. Again the compound of formula R¹R²M′X′₂ maybe free in the reaction solution or immobilized on a solid support suchas a polymer support, where the groups R¹ and R² then constitute aportion of the polymer or are otherwise coupled to the polymer (withimmobilization on the solid support facilitating the subsequentseparation of the acylated dipyrromethane product).

Making chlorins. A further aspect of the present invention is a methodof making a compound useful as a chlorin eastern half, comprising:providing a 1-monoacyldipyrromethane-boron complex as described above,and then halogenating (e.g., brominating) said 1-monoacyldipyrromethanein said complex at the 9 position to produce a1-acyl-9-bromodipyrromethane boron complex useful as a chlorin easternhalf, or substituting the 1-monoacyldipyrromethane at the 9 positionwith alkoxy or acetoxy as described in U.S. Pat. No. 6,559,374. Anyhalogenating agent may be used, including but not limited toN-chlorosuccinimide, N-bromosuccinimide, N-iodosuccinimide,1,3-dichloro-5,5-dimethylhydantoin, 1,3-dibromo-5,5-dimethylhydantoin,chlorine, bromine, and iodine. The reaction is preferably carried out ata temperature less than room temperature, most preferably 0 to −100° C.,in any suitable solvent such as tetrahydrofuran, dioxane, diethyl etheror other ethereal solvents, but preferably THF. The method may thenfurther comprise the steps of condensing said1-acyl-9-halodipyrromethane boron complex (containing the eastern half)(particularly the reduction product, i.e., the carbinol, derived fromthe I-acyl-9-substituted dipyrromethane boron complex) with a chlorinwestern half (typically in an organic solvent in the presence of anacid) to form a condensation product; and then oxidatively cyclizingsaid condensation product (typically in an organic solvent in thepresence of a base, an oxidant and a metal salt) to produce a chlorin.The terms “Eastern half” and “Western half” are known in the art ofchlorin chemistry; reactions for producing a chlorin from eastern andwestern halves are known in the art of chlorin chemistry, and can becarried out in accordance with known techniques or variations thereofwhich will be apparent to those skilled in the art given the presentdisclosure. See, e.g., U.S. Pat. No. 6,559,374 to Lindsey andBalasubramanian.

Utility. 1-Acyldipyrromethanes are essential intermediates in thesynthesis of trans-A₂B₂, trans-AB₂C, cis-A₂B₂, cis-AB₂C, and ABCDporphyrins; diverse chlorins; A₂B, AB₂, and ABC corroles; and bilanes.The boron-complexation strategy provides a facile method for theisolation of a 1-acyldipyrromethane from the crude acylation mixture.The boron-complexation strategy can be used for the purification of awide variety of 1-acyldipyrromethanes. The 1-acyldipyrromethane-boroncomplexes can be decomplexed to give the 1-acyldipyrromethanes in goodto excellent yields. Alternatively, reduction of a1-acyldipyrromethane-boron complex followed by self-condensation of theresulting dipyrromethane-carbinol affords the corresponding trans-A₂B₂porphyrin. The ability to isolate and handle 1-acyldipyrromethanes asdialkylboron complexes should increase the scale of 1-acyldipyrromethanesyntheses and facilitate the preparation of a wide variety ofporphyrinic compounds.

1-Acyldipyrromethanes produced as described herein can be used as anintermediate for the production of a variety of useful compounds, suchas 1,9-diacyldipyrromethanes, which are in turn useful for theproduction of compounds such as porphyrin ring compounds or porphyrinicmacrocycles. The porphyrinic macrocycles are useful, among other things,for the production of polymers thereof which may be immobilized orcoupled to a substrate and used as light harvesting rods, lightharvesting arrays, and solar cells, as described for example in U.S.Pat. No. 6,407,330 to Lindsey et al. or U.S. Pat. No. 6,420,648 toLindsey. Porphyrinic macrocycles are also useful immobilized to asubstrate for making charge storage molecules and information storagedevices containing the same. Such charge storage molecules andinformation storage devices are known and described in, for example,U.S. Pat. No. 6,208,553 to Gryko et al.; U.S. Pat. No. 6,381,169 toBocian et al.; and U.S. Pat. No. 6,324,091 to Gryko et al. Theporphyrinic macrocycle may comprise a member of a sandwich coordinationcompound in the information storage molecule, such as described in U.S.Pat. No. 6,212,093 to Li et al. or U.S. Pat. No. 6,451,942 to Li et al.

The present invention is explained in greater detail in the followingnon-limiting Examples.

EXAMPLES

The synthesis of a 1-acyldipyrromethane (2) is achieved by treatment ofa dipyrromethane (1) with EtMgBr in THF at room temperature followed byaddition of a pyridyl thioester (5) in THF at −78° C.² The productmixture consists of unreacted dipyrromethane (1), the1-acyldipyrromethane (2), and pyridyl thioester and/or other byproducts(Scheme 1). A suitable complexation aid for application to such amixture should meet several criteria, including at least some of thefollowing: (1) afford reaction with diverse 1-acyldipyrromethanes, (2)resist complex formation with other species in the reaction mixture,particularly the dipyrromethane, (3) yield a crystalline solid, (4)exhibit sufficient stability for routine handling, and (5) undergodecomplexation under mild conditions to liberate the1-acyldipyrromethane in pure form.

A number of metal complexes of 2-acylpyrroles are known, as shown inChart 3. Pyrrole-2-carboxaldehyde forms a stable coordination complex(A) in conjunction with acetylacetone and copper(II), nickel(II),palladium(II), or platinum(II).⁸ Pyrrole-2-carboxaldehyde and iminoderivatives therefrom also form complexes with various metals orcoordination centers (B,⁹ C,¹⁰ D,¹¹ E,¹⁰ and F¹²). We began our searchfor suitable metal complexes of 1-acyldipyrromethanes on the basis ofthe known complexes of 2-acylpyrroles. Note that 1-acyldipyrromethanesand 2-acylpyrroles each contain the same α-acylpyrrole motif.

Results and Discussion

Identification of Suitable 1-Acyldipyrromethane-Coordination Complexes.A variety of metal reagents were examined as potential complexation aidsfor 1-acyldipyrromethanes. The metals include Mg(OAc)₂.4H₂O, Sc(OTf)₃,TiF₄, MnCl₂, Mn(OAc)₂, FeBr₃, Fe(OAc)₂, Fe(acac)₃, Co(OAc)₂.4H₂O,Ni(OAc)₂.4H₂O, Cu(OAc)₂—H₂O, Zn(OAc)₂.2H₂O, GeI₄, MoCl₃, RuCl₃H₂O,Pd(OAc)₂, Pd(CH₃CN)₂Cl₂, Ag(OTf), CdCl₂, InCl₃, In(OAc)₃, SnF₄, SbCl₅,TeCl₄, CeI₃, EuCl₃, Dy(OTf)₃, Yb(OTf)₃, Tl(OAc), and BiCl₃. Theconditions employed treatment of a methanolic solution of 2a² (100 mM)with the metal reagent (50 mM) at room temperature for 1 h. Most of thereagents examined gave multiple components. A readily isolable complexwas obtained only with Cu(OAc)₂.H₂O, affording Cu-2a as a greenprecipitate (Scheme 2). While the formation of Cu-2a was promising,copper was found to have three limitations as a complexing agent: (1)the Cu-2a complex underwent decomplexation upon silica TLC; (2)formation of the complex was quite substrate selective: a copper complexwas obtained for 1-p-toluoyl-5-phenyldipyrromethane (2a) but not with1-pentafluorobenzoyl-5-(pentafluorophenyl)dipyrromethane (2e)¹; and (3)the Cu-2a complex was an amorphous solid rather than a crystallineproduct.

1-Acyldipyrromethane-Boron Complexes. To meet the objectives of broadapplicability and formation of crystalline products, we turned toinvestigate boron complexes. The first boron derivative of adipyrromethane species apparently was reported by Treibs et al.¹³ whoreacted BF₃-etherate with a dipyrrin to obtain a difluoroboron-dipyrrincomplex. A wide variety of such difluoroboron-dipyrrin (BODIPY)derivatives have been prepared owing to their high fluorescenceyields.¹⁴ The boron-difluoride complexes of dipyrrins are exceptionallyresistant to decomplexation.¹³⁻¹⁵ 2-Ketopyrroles are also known to formstable boron-difluoride complexes (G, Chart 3).¹⁵ A dialkylboron complexof a 2-iminopyrrole also is known (H, Chart 3).¹⁶

We thought that boron complexes with B,B-dialkyl substituents mightafford the appropriate balance of stability and susceptibility todecomplexation for our studies. A variety of compounds containingN-(dialkylboryl)pyrrole¹⁷⁻²⁵ or N-(diarylboryl)pyrrole²⁶ motifs havebeen prepared. Thus, reaction of 2a and Bu₂B-OTf in CH₂Cl₂ containingTEA at room temperature afforded the corresponding boron complex 6a-BBu₂in 93% yield (Scheme 3). The boron complex was readily isolated bypassage through a pad of silica. The generality of the complexation of1-acyldipyrromethane 2a with various boron reagents was examined. Thecomplex of 2a with 9-BBN gave an orange-yellow solid whereas the boroncomplex with dibutyl or dimethyl substituents gave an orange oil. On theother hand, no complex was obtained with BF₃.O(Et)₂ or B-bromocatecholborane. Owing to the high yield and formation of a crystalline product,we primarily used 9-BBN complexes for further study.

Scheme 3

R₂B X Complex Yield Bu₂B OTf 6a-BBu₂ 93% Me₂B Br 6a-BMe₂ 91% 9-BBN OTf6a-BBN 94% F₂B F 6a-BF₂  0% B-Catechol Br 6a-B(cat)  0%

The selectivity of boron complexation was examined next. Dipyrromethane1a did not give a boron complex (TLC analysis). However, a trace amountof an oxidized derivative, tentatively assigned as dipyrrinato-boroncomplex 7, was observed. The reaction of 1,9-diacyldipyrromethane 3a¹and Bu₂B-OTf in CH₂Cl₂ containing TEA at room temperature afforded thecorresponding bis-boron complex 3a-(BBu₂)₂ (Scheme 4).

The generality of the complexation with 9-BBN-OTf was examined withvarious 1-acyldipyrromethanes (Scheme 5). The requisite1-acyldipyrromethanes 2a,² 2d,⁷ 2e,¹ 2f,² 2g,¹ 2h,⁷ and 2i²⁷ are knowncompounds while 2b and 2c were prepared herein following the generalmethod.² In each case, the resulting boron complex was hydrophobic andeasily isolated by passage through a pad of silica. The complexation of1-acyldipyrromethanes 2a–2d and 2g with 9-BBN-OTf gave 6a-BBN-6d-BBN and6g-BBN in excellent yields (87–97%). The reaction of 2e or 2f with9-BBN-OTf gave complete reaction (TLC analysis), but partialdecomplexation occurred upon passage through a silica pad, affording amixture of 2e and 6e-BBN or 2f and 6f-BBN. The instability of the bulky,mesityl-substituted complex 6f-BBN was circumvented by reaction of 2fwith Bu₂B-OTf, which gave 6f-BBu₂ as a stable product in 89% yield. Thesame approach with the pentafluorophenyl-substituted 2e gave 6e-BBu₂,which was isolated in pure form by silica pad separation but underwentfacile decomplexation to 2e upon further handling.

Scheme 5

2 R¹ R² R₂B Product (Yield) 2a

9-BBN 6a-BBN (94%) 2b

9-BBN 6b-BBN (91%) 2c

9-BBN 6c-BBN (87%) 2d

9-BBN 6d-BBN (97%) 2e

9-BBNBu₂B 6e-BBN^(a)6e-BBu₂ (97%) 2f

9-BBNBu₂B 6f-BBN^(a)6f-BBu₂ (89%) 2g

9-BBN 6g-BBN (96%) 2h

9-BBNBu₂B 6h-BBN (93%)6h-BBu₂ (90%) 2i

9-BBNBu₂B 6i-BBN^(a)6i-BBu₂ (89%) ^(a)The product partially decomplexedupon chromatography.

To check the effect of the presence of a single pentafluorophenyl groupat the 5- or 1-position, boron complexation reactions of 2h and 2i wereinvestigated. The reaction of 2h (5-pentafluorophenyl substituent) with9-BBN-OTf or Bu₂B-OTf gave a stable complex (6h-BBN or 6h-BBU₂) inexcellent yield. However, reaction of 2i (1-pentafluorobenzoylsubstituent) with 9-BBN-OTf gave a complex (6i-BBN) that proved unstablewhereas the reaction of 2i with 9-BBu₂-OTf gave 6i-BBu₂ in 89% yield.Thus, the presence of the pentafluorophenyl group is deleterious only atthe 1-acyl position.

It is noteworthy that almost all 9-BBN complexes of1-acyldipyrromethanes were solids (the all-pentyl 6c-BBN was the oneexception). On the other hand, almost all dibutylboron complexes of1-acyldipyrromethanes were oils (6f-BBu₂ was the one exception).Regardless of state, the complexes are yellow-orange whereas theuncomplexed 1-acyldipyrromethanes are off-white solids. The1-acyldipyrromethane-boron complexes are stable to water and routinehandling. Unlike 1-acyldipyrromethanes, the 1-acyldipyrromethane-boroncomplexes can be precipitated/crystallized from CH₂Cl₂/hexanes, arerelatively non-polar, and do not streak upon chromatography.

Characterization. The spectral changes upon boron complexation of a1-acyldipyrromethane include the presence of the characteristicabsorption at ˜340–390 nm. The ¹H NMR spectra show (1) disappearance ofthe NH resonance of the acylpyrrole unit, (2) a ˜0.4 ppm upfield shiftof the unsubstituted pyrrolic NH resonance, (3) a downfield shift of themeso-proton (˜0.2 ppm), and (4) a downfield shift of the β-protons (˜1ppm) of the acylpyrrole. The ¹³C NMR spectra show the downfield shift ofthe carbonyl carbon (˜8 ppm). The ¹¹B NMR spectra of selected samples(6a-BBN–6d-BBN, and 6g-BBN) each showed a single peak at ˜13 ppm,relative to the ¹¹B standard, BF₃.O(Et)₂ (0 ppm). For comparison, theboron signal in the unacylated N-(9-borabicyclo[3.3.1]non-9-yl)pyrroleappears at 59.9 ppm.²³ The relative upfield shift of the acylatedpyrrole is characteristic of organoboron species with coordination inthe lone p orbital of the boron atom.²⁸ Elemental analyses for some ofthe boron complexes were satisfactory while others showed unsatisfactoryresults for carbon. This discrepancy may stem from solvent inclusion inthe crystal lattice of the boron complexes. However, FABMS analyses ofthese complexes were satisfactory.

X-ray structural analysis was performed on 6a-BBN (FIG. 1). Complexationresults in near coplanarity of the boron atom, α-carbonyl, and pyrroleunit. The C—O bond length (1.298 Å) is longer than for that in2-benzoylpyrrole (1.234 Å),²⁹ suggesting some enolate character. At thesame time, the C—C bond between the carbonyl carbon and the α-carbon ofthe acylpyrrole (1.402 Å) is significantly shorter than for that in2-benzoylpyrrole (1.445 Å)²⁹ suggesting partial multiple bond character.Similar structural features were reported for the 2-ketopyrrole-BF₂complex.¹⁵

Boron Complexation as a Purification Aid for 1-Acyldipyrromethanes. Anintegrated procedure consisting of 1-acylation and subsequent boroncomplexation was developed. The two steps are carried out as follows:

The dipyrromethane (1) is treated with 2.0 molar equiv of EtMgBrfollowed by 1.0 molar equiv of a Mukaiyama reagent³⁰ (5). The reactionmixture is quenched with aqueous NH₄Cl, and the organic layer isseparated and concentrated, affording the crude product 2 (vide infra).Note that the use of boron complexation to isolate the1-acyldipyrromethane enables use of a stoichiometric quantity of EtMgBr,rather than an excess as employed previously to ensure completeconsumption of the Mukaiyama reagent.²

The residue (2) is dissolved in CH₂Cl₂ and treated with TEA and R₂B-OTfat room temperature for 1 h. Passage of the reaction mixture over a padof silica using CH₂Cl₂/hexanes as eluant readily affords the boroncomplex.

In this manner, a series of dipyrromethanes (1a–f,³¹ 1g³²) was reactedwith the appropriate Mukaiyama reagent (5a–e², 5f³³) followed by boroncomplexation with Bu₂B-OTf or 9-BBN-OTf. The boron complexes of 2a–2cand 2f-2h were readily obtained in good yield (Scheme 6).

Scheme 6

1 + 5 R¹ R² R₂B Product (Yield) 1a + 5a

9-BBN 6a-BBN (67%) 1b + 5a

9-BBN 6b-BBN (60%) 1c + 5f

9-BBN 6c-BBN (60%) 1d + 5b

9-BBN 6d-BBN (66%) 1f + 5d

Bu₂B 6f-BBu₂ (68%) 1g + 5e

9-BBn 6g-BBN (71%) 1e + 5a

9-BBN 6h-BBN (58%)

A slight modification to the general boron-complexation method wasexplored to further minimize use of chromatography. The modificationentails use of a solvent for complexation that results in precipitationof the 1-acyldipyrromethane-boron complex. Thus, the reaction of 2a with9-BBN-OTf in the presence of TEA in toluene afforded a precipitate,which largely consisted of 6a-BBN and the TfOH.TEA salt. Washing withwater and methanol afforded the desired 1-acyldipyrromethane-boroncomplex 6a-BBN. This procedure was employed with 8.88 g of 2a, affordinga precipitate (9.63 g, 52%) of analytically pure 6a-BBN. Silica padseparation of the filtrate afforded additional material (1.77 g), givingan overall yield of 62%. This procedure is well suited for synthesis atthe multigram level. Note that no change in solvent was required for usewith 2d; the boron complex 6d-BBN precipitated upon formation in CH₂Cl₂.Note that dipyrromethanes 1a–f were prepared by a streamlined procedurewith minimal or no reliance on chromatography,³¹ and 1g was preparedherein by the same procedure; accordingly, the overall route to form a1-acyldipyrromethane can now be implemented with limited or no use ofchromatography.

Decomplexation of 1-Acyldipyrromethane-Boron Complex. A simple methodfor decomplexation of the 1-acyldipyrromethane-boron complexes wasinvestigated using 6a-BBN as a test case. The cleavage of the B—N bondin alkyl or aryl amines has been achieved with acids,^(34,35) bases,³⁵or ethanolamine.³⁵ The similar cleavage of N-(dialkylboron)pyrroles hasbeen achieved with acids^(19,24) or ethanol.²⁴ Given the potentiallability of the 1-acyldipyrromethane to acidic conditions, we focused onneutral reaction conditions. Smooth decomplexation was obtained inrefluxing solvents composed of H₂O/THF or ROH/THF, where ROH ismethanol, neopentyl glycol, ethanolamine, polyethylene glycol,1,3-propanediol, pentaerythritol or polyvinyl alcohol. In many cases,isolation could be achieved in nearly pure form without chromatography.A key factor in choice of alcohol is to avoid chromatography altogetherfor separation of the 1-acyldipyrromethane and the derivative formedupon reaction of ROH and the dibutylboron or 9-BBN species. We foundthat 1-pentanol generally afforded superior results. Accordingly,treatment of 6a-BBN with excess I-pentanol in refluxing THF for 1 hfollowed by solvent removal, trituration with hot hexanes for 5 min, andrecrystallization/precipitation from CH₂Cl₂/hexanes afforded 2a in 83%yield (Scheme 7).

Scheme 7

6a-BR₂ R¹ R² R₂B Product (Yield) 6a-BBN

9-BBN 2a (83%) 6b-BBN

9-BBN 2b (81%) 6c-BBN

9-BBN 2c (82%) 6d-BBN

9-BBN 2d (80%) 6f-BBu₂

Bu₂B 2f (65%)

Application of these decomplexation conditions to 6a-BBN, 6b-BBN, and6d-BBN afforded 2a, 2b, and 2d, respectively in excellent yields (Scheme7). The boron complex 6f-BBu₂ was decomplexed with neat 1-pentanol at80° C. for 1 h followed by the workup procedure described above.Decomplexation of 6c-BBN with 1-pentanol in THF at reflux for 1 hafforded 2c, which was isolated upon passage through a pad of alumina.

Use of 1-Acyldipyrromethane-Boron Complexes in Porphyrin Formation. Thereduction of a 1-acyldipyrromethane affords the correspondingdipyrromethane-1-carbinol, which upon self-condensation and oxidationaffords the trans-A₂B₂ porphyrin.^(2,33) The 1-acyldipyrromethane-boroncomplexes were examined as precursors to trans-A₂B₂ porphyrins, therebyavoiding the boron-decomplexation procedure. Thus, the boron complex6a-BBu₂ was treated with NaBH₄ in THF/methanol for 40 min. TLC analysisindicated complete consumption of 6a-BBu₂ and formation of a new polarspot. The reaction mixture was worked up in the standard way and theproduct was subjected to acid-catalyzed self-condensation [Yb(OTf)₃ inCH₂Cl₂]³³ followed by oxidation with DDQ. Porphyrin 8 was obtained in26% yield (Scheme 8). The boron complex 6a-BBN was treated similarly, 5affording porphyrin 8 in 17% yield. In both cases, no other porphyrinspecies were observed upon LD-MS³⁶ analysis of the crude reactionmixtures. For comparison, the reaction of the uncomplexed1-acyldipyrromethane 2a affords porphyrin 8 in 25% yield.³³

9-Acylation of 1-Acyldipyrromethane-Boron Complexes. The acylation ofdipyrromethanes to form 1,9-diacyldipyrromethanes is an essential stepin the rational synthesis of porphyrins. Dipyrromethanes with identicalacyl groups at the 1- and 9-positions are key precursors to A₃B-,trans-A₂B₂-, and trans-AB₂C-porphyrins. Dipyrromethanes bearing twodifferent acyl groups at the 1- and 9-positions are required precursorsto cis-A₂B₂-, cis-A₂BC- and ABCD-porphyrins. Reaction of a1-acyldipyrromethane (2) with EtMgBr and an acid chloride affords the1,9-diacyldipyrromethane (3).¹ Other methods (Friedel-Crafts, Vilsmeier,benzoxathiolium salt) also have been examined for the 9-acylation of a1-acyldipyrromethane.⁷ Regardless of synthetic method, purification ofacyldipyrromethane is difficult because acyldipyrromethanes (2 or 3)typically streak extensively upon chromatography and give amorphouspowders upon attempted crystallization.

While the 1-acylation of dipyrromethanes proceeds well with yields of˜80–90%, the 9-acylation has proved more problematic and generallyafforded yields of ≦60%. The difficulty with the second acylation, whilepuzzling, has led to use of a more potent acylating agent (e.g., an acidchloride) than the pyridyl thioate (Mukaiyama reagent)³⁷ employed forthe 1-acylation. A more fundamental limitation stem from the requirementfor the presence of a base to neutralize the HCl liberated uponacylation. In principle, 3 equiv of EtMgBr and 1 equiv of acid chlorideare needed for the reaction, but in practice,¹ 6 equiv of EtMgBr and 3equiv of acid chloride are employed. Attempts to use various bases otherthan EtMgBr have generally afforded little improvement in the yield ofthe 1,9-diacyldipyrromethane.

Here we describe our studies on the use of 1-acyldipyrromethane-BR₂complexes as acylation substrates. 9-BBN complexes were chosen becauseof their high crystallinity, however other dialkylboron complexes alsocan be used. We chose the reaction of 6a-BBN and S-2-pyridyl4-methylbenzothioate (5a) as a model system for optimization ofconditions. Thus, a solution of 6a-BBN (0.10 mmol, 1.0 M) in toluene atroom temperature was treated with EtMgBr (0.15 mmol) followed by 5a(0.10 mmol, 1.0 M) in toluene (0.1 mL) (Scheme 9).

TLC and ¹H NMR analysis indicated the presence of equal amounts (˜1:1)of the desired 1,9-diacyldipyrromethane-BR₂ complex (3a-BBN) and thestarting 1-acyldipyrromethane-BR₂ complex (6a-BBN) (entry 1, Table 1).The yield was determined by ¹H NMR spectroscopic analysis of crudereaction samples by comparing the peak intensity for the H³ protonsignals for 1,9-diacylated (˜6.46 ppm) and 1-acylated (˜6.41 ppm)dipyrromethane-BR₂ complexes (Chart 4).

The use of THF rather than toluene as a solvent improved the relativeyield of the 1,9-diacyldipyrromethane-BR₂ complex (˜1.7:1.0; entry 2).Use of p-toluoyl chloride rather than the Mukaiyama reagent gaverelatively little reaction (˜0.4:1.0; entry 3). Use of 1 equiv of EtMgBrreduced the yield of the 1,9-diacyldipyrromethane-BR₂ complex (˜1.1:1.0;entry 4). A limiting yield of 50% is expected considering that theliberated products (3a-BBN and pyridylthiol) are more acidic than thestarting material (6a-BBN), causing decomposition of the 6a-BBN-MgBrcomplex. On the other hand, use of excess EtMgBr is expected to beineffective owing to the competive reaction of the Grignard reagent withMukaiyama reagent (entry 5), forming the ketone. Indeed, the Mukaiyamareagents were initially developed for the synthesis of ketones.³⁷

TABLE 1 Conditions for the 9-acylation of 1-acyldipyrromethanesSubstrate Solvent EtMgBr^(a) RCOX^(b) Entry (cmpd, mmol) (mL) Base(mmol) (mmol) Temperature (mmol) Product:Substrate^(c) 1 6a-BBN, 0.10Toluene (0.1) — 0.15 RT 0.10 1.0:1.0 2 6a-BBN, 0.10 THF (0.1) — 0.15 RT0.10 1.7:1.0 3 6a-BBN, 0.10 THF (0.2) — 0.15 RT 0.11^(d) 0.4:1.0 46a-BBN, 0.10 THF (0.1) — 0.10 RT 0.10 1.1:1.0 5 6a-BBN, 0.10 THF (0.1) —0.25 RT 0.10 1.0:1.0 6 6a-BBN, 0.10 THF (0.2) TMP (0.10) 0.20 0° C. → RT0.10 2.1:1.0 7 6a-BBN, 0.10 THF (0.2) Dicyclohexylamine (0.10) 0.20 0°C. → RT 0.10 2.3:1.0 8 6a-BBN, 0.10 THF (0.2) HMDS (0.10) 0.20 0° C. →RT 0.10 4.0:1.0 9 2a, 0.10 THF (0.10) — 0.20 RT 0.20 0.3:1.0 10 2a, 0.10THF (0.20) HMDS (1.0) 0.30 0° C. → RT 0.20 0.6:1.0 ^(a)EtMgBr was usedas a 1.0 M solution in THF. ^(b)S-2-Pyridyl 4-methylbenzothioate (5a).^(c)The ratio was determined by ¹H NMR spectroscopic analysis of crudereaction samples. ^(d)p-Toluoyl chloride instead of 5a.

To overcome these problems we considered using a base whose conjugateacid (Base-H) has higher pK_(a) than that of the liberated products(3a-BBN and pyridylthiol) and starting material 6a-BBN. Thus therequirement for the base strength is as followsEt-MgBr>Base-MgBr>pyrrole-MgBr>acylpyrrole-MgBr>pyridylthiolate-MgBr,where X—MgBr refers to the Grignard reagent formed from the conjugatebase of the weak acid XH. In other words the conjugate acid of the baseshould have a pK_(a) greater than that of pyrrole (˜17.5) and less thanthat of ethane (˜45). In addition the base should be non-nucleophilic.For such non-nucleophilic bases, we examined2,2,6,6-tetramethylpiperidine (TMP), dicyclohexylamine and1,1,1,3,3,3-hexamethyldisilazane (HMDS), which have pK_(a) values³⁸ of37, 36 and 26, respectively (entry 6–8). A significant improvement wasobtained with use of 2,2,6,6-tetramethylpiperidine or dicyclohexylamine(˜2:1; entries 6 and 7). Even greater improvement was obtained withHMDS, which gave a 4:1 ratio of 1,9-diacyl to 1-acyldipyrromethaneproducts (entry 8).

A comparative study with an uncomplexed 1-acyldipyrromethane wasperformed using similar conditions with and without additional base.Thus, a solution of 1-(p-toluoyl)-5-phenyldipyrromethane (2a) (0.10mmol) in THF (0.1 mL, 1.0 M) at room temperature was treated with EtMgBr(0.20 mmol) followed by 5a (0.10 mmol) in THF (0.1 mL, 1.0 M). TLC and¹H NMR analysis indicated the presence of the desired1,9-diacyldipyrromethane (3a) and the starting 1-acyldipyrromethane (2a)in only a 0.3:1 ratio (entry 9, Table 1). The ratio of1,9-diacyldipyrromethane (3a) to the starting 1-acyldipyrromethane (2a)was improved slightly (˜0.6:1) by treating 2a (0.10 mmol) in THF (0.1mL) and HMDS (0.10 mmol) with EtMgBr (0.30 mmol) followed by addition of5a (0.20 mmol) in THF (0.20 mL, 1.0 M) (entry 10, Table 1). While theaddition of HMDS afforded an improvement in the yield, the presence ofthe non-nucleophilic buffering agent alone was insufficient to afford ahigh yield with the uncomplexed 1-acyldipyrromethane. The origin of thelow yield of the reaction with the uncomplexed 1-acyldipyrromethane maystem from poor reactivity in an aggregate, or complexation of the twoneighboring pyrrolic species in the 1-acyldipyrromethane. This procedurewherein a mixture of 1-acyldipyrromethane-BR₂ complex (6-BR₂) (1 equiv)and HMDS (1 equiv) is treated with EtMgBr (2 equiv) followed by additionof Mukaiyama reagent (5) (1 equiv) in THF affords a superior yield ofthe corresponding 1,9-diacyldipyrromethane-BR₂ complex (3-BR₂).Moreover, the method enables use of the more gentle Mukaiyama reagentsrather than acid chlorides for acylation.

On the basis of these observations we propose the following mechanism.The 1-acyldipyrromethane-BR₂ complex (6-BR₂) in principle requires only1 equiv of EtMgBr owing to the absence of the NH (i.e. the protectionafforded by the R₂B entity) to form the pyrrole-MgBr species. A secondequiv of EtMgBr is used to make the non-nucleophilic buffering agentBase-MgBr, the Grignard derivative of the base. The pyrrole-MgBr speciesthen reacts with the Mukaiyama reagent to give the acylpyrrolic-MgBr andpyridylthiol as a byproduct. Base-MgBr then reacts with pyridylthiol togive pyridylthiolate-MgBr and Base-H again. Note that like EtMgBr,Base-MgBr might also exist in a Schlenk equilibrium. Indeed, it is knownthat the Grignard derivative of HMDS exists in a multimeric complex.³⁹

It is noteworthy that the requirement for the presence of a “bufferingagent” is less onerous in the synthesis of acylpyrroles. Indeed, inNicolaou's synthesis of 2-acylpyrroles using the pyrrolic Grignardreagent and a Mukaiyama reagent, six equivalents of the pyrrolicGrignard reagent were employed.⁴⁰ In those syntheses, the Mukaiyamareagent was the more valuable species. In the synthesis of1,9-diacyldipyrromethanes, the 1-acyldipyrromethane is a valuableintermediate and not available in excess, but the Grignard reagent ofHMDS provides a suitable buffering agent.

Use of 1,9-Diacyldipyrromethane-Boron Complexes for Porphyrin Formation.The 1,9-diacyldipyrromethane-boron complex 3a-BBN was examined as aprecursor in a porphyrin-forming reaction. Thus, the boron complex3a-BBN was treated with NaBH₄ in THF/methanol for 40 min. The reactionmixture was worked up in the standard way^(1,2) and the product wassubjected to acid-catalyzed condensation with dipyrromethane 1a followedby oxidation with DDQ. The corresponding porphyrin 8 was obtained in 20%yield. No other porphyrin species were observed upon LD-MS analysis ofthe crude reaction mixture.

Bromination of a 1-Acyldipyrromethane-Boron Complex.1-Bromo-9-acyldipyrromethanes are precursors for the synthesis ofchlorin building blocks.⁴ A 1-bromo-9-acyldipyrromethane is prepared bybromination of a 1-acyldipyrromethane. Treatment of 6a-BBN with NBS inTHF at −78° C. for 1 h afforded the desired 1-bromo-9-acyldipyrromethaneas the 9-BBN complex 9a-BBN in 94% yield (Scheme 10).

Experimental Section:

Noncommercial Compounds: Dipyrromethanes 1a–1f were prepared asdescribed in the literature and analyzed for purity by gaschromatography.³¹ 1-Acyldipyrromethanes 2a,² 2d,⁷ 2e,¹ 2f,² 2g,¹ 2h,⁷2i,²⁷ and 3a¹ and the Mukaiyama reagents 5a–5e,2 and 5f³³ were preparedas described in the literature.

5-[4-(Trimethylsilylethynyl)phenyl]dipyrromethane (1g). Following astandard procedure,³¹ a solution of4-(trimethylsilylethynyl)benzaldehyde (7.00 g, 35.0 mmol) in pyrrole(347 mL) was degassed for 10 min. Then InCl₃ (1.11 g, 5.00 mmol) wasadded. The mixture was stirred at room temperature under argon. After1.5 h, NaOH (6.00 g, 0.15 mol, 20–40 mesh beads) was added and thestirring was continued for an additional 45 min. The mixture wasfiltered and the filtrate was concentrated under high vacuum. Theresulting oil was triturated with hexanes (50 mL), and the volatilecomponents were evaporated. This procedure was repeated four times,affording a white solid. Crystallization from ethanol afforded off-whitecrystals (7.66 g, 69%): mp 122–123° C. (lit.³² 120° C.); ¹H NMR spectraldata are consistent with reported values:³² ¹H NMR δ 0.26 (s, 9H), 5.45(s, 1H), 5.88–5.92 (m, 2H), 6.13–6.19 (m, 2H), 6.67–6.71 (m, 2H), 7.14(d, J=8.0 Hz, 2H), 7.42 (d, J=8.0 Hz, 2H), 7.83–7.90 (br, 2H); Anal.Calcd for C₁₈H₂₀N₂: C, 75.42; H, 6.96; N, 8.80, Found: C, 75.40; H,6.88; N, 8.75.

1-(4-Methylbenzoyl)dipyrromethane (2b). Following a standard procedure²(but with a 500 mM solution of 1b rather than 1 M owing to limitedsolubility), a solution of 1b (0.731 g, 5.00 mmol) in THF (10 mL) atroom temperature under argon was treated with EtMgBr (12.5 mL, 12.5mmol, 1.0 M solution in THF) for 10 min. The solution was cooled to −78°C. Then a solution of 5a (1.15 g, 5.00 mmol) in THF (5.0 mL) was added.The reaction mixture was stirred at −78° C. for 10 min and at roomtemperature for 20 min. Standard workup and chromatography [silica,CH₂Cl₂/ethyl acetate (9:1)] afforded a pale brown solid (0.812 g, 62%):mp 172–174° C.; ¹H NMR δ 2.43 (s, 3H), 4.09 (s, 2H), 6.03–6.06 (m, 1H),6.08–6.12 (m, 1H), 6.14–6.18 (m, 1H), 6.51–6.55 (m, 1H), 6.80–6.86 (m,1H), 7.27 (d, J=8.0 Hz, 2H), 7.76 (d, J=8.0 Hz, 2H), 9.25–9.28 (br, 1H),10.94–10.98 (br, 1H); ¹³C NMR δ 21.8, 26.8, 106.4, 108.3, 110.3, 117.7,123.1, 128.2, 129.3, 130.7, 136.0, 141.2, 142.7, 185.6; Anal. calcd forC₁₇H₁₆N₂O: C, 77.25; H, 6.10; N, 10.60. Found: C, 76.52; H, 5.89; N,10.33.

1-Hexanoyl-5-pentyldipyrromethane (2c). Following a standard procedure,²a solution of 1c (1.08 g, 5.00 mmol) in THF (5.0 mL) under argon at roomtemperature was treated with EtMgBr (12.5 mL, 12.5 mmol, 1.0 M solutionin THF) for 10 min. The solution was cooled to −78° C. Then a solutionof 5f (1.05 g, 5.00 mmol) in THF (5.0 mL) was added. The reactionmixture was stirred at −78° C. for 10 min and at room temperature for 20min. Standard workup and chromatography [silica, CH₂Cl₂/ethyl acetate(9:1)] afforded a light yellow oil (0.986 g, 63%): ¹H NMR δ 0.81–0.90(m, 6H), 1.22–1.37 (m, 10H), 1.68–1.76 (m, 2H), 2.00–2.06 (m, 2H), 2.74(t, J=7.6 Hz, 2H), 4.05 (t, J=7.6 Hz, 1H), 6.02–6.06 (m, 1H), 6.08–6.14(m, 2H), 6.64–6.68 (m, 1H), 6.88–6.91 (m, 1H), 8.94–8.98 (br, 1H),10.16–10.20 (br, 1H); ¹³C NMR δ 14.1, 14.2, 22.7, 26.2, 27.7, 31.85,31.87, 33.8, 38.1, 38.3, 105.0, 108.1, 108.5, 117.3, 119.5, 131.1,133.0, 144.8, 191.9; Anal. calcd for C₂₀H₃₀N₂O: C, 76.39; H, 9.62; N,8.91. Found: C, 76.15; H, 9.80; N, 8.77.

Screening Protocol for Metal Complexation of 1-Acyldipyrromethanes. Asolution of 2a (0.017 g, 0.050 mmol) in methanol (0.5 mL) was treatedwith a solution of a metal reagent (0.025 mmol) in methanol (0.5 mL).The mixture was stirred at room temperature for 1 h. The reaction wasmonitored visually for precipitate formation. The reaction mixture wasexamined by TLC (silica, CH₂Cl₂/ethyl acetate, 9:1) and by absorptionspectroscopy.

Bis[1-(4-methylbenzoyl)-5-phenyldipyrromethan-10-yl]copper(II) (Cu-2a).A solution of 2a (0.25 mmol, 85 mg) in methanol (2.5 mL) was treatedwith a warm solution of Cu(OAc)₂.H₂O (0.30 mmol, 26 mg) in methanol (1mL). The mixture was stirred at room temperature for 20 min. Theresulting precipitate was filtered. The filtered material was washedwith methanol and dried in vacuo to afford a green powder (75 mg, 81%):Anal. calcd for C₄₆H₃₈CuN₄O₂: C, 74.42; H, 5.16; N, 7.55. Found: C,73.93; H, 5.22; N, 7.40; λ_(abs) 380 nm.

10-(Dibutylboryl)-1-(4-methylbenzoyl)-5-phenyldipyrromethane (6a-BBu₂).A solution of 2a (0.340 g, 1.00 mmol) in CH₂Cl₂ (2 mL) was treated withTEA (0.335 mL, 2.40 mmol) followed by Bu₂B-OTf (2.00 mL, 2.00 mmol, 1.0M in CH₂Cl₂). After 30 min, the mixture was passed through a pad ofsilica (4×8 cm) eluting with CH₂Cl₂. The product eluted as a fast-movingyellow band, which upon concentration afforded an orange oil (0.431 g,93%): ¹H NMR δ 0.36–0.52 (m, 2H), 0.61 (t, J=7.2 Hz, 3H), 0.65–1.18 (m,13H), 2.47 (s, 3H), 5.60 (s, 1H), 5.85–5.88 (m, 1H), 6.13–6.17 (m, 1H),6.45 (d, J=4.0 Hz, 1H), 6.68–6.72 (m, 1H), 7.20–7.38 (m, 8H), 7.79–7.83(br, 1H), 8.11 (d, J=8.0 Hz, 2H); ¹³C NMR δ 14.3, 14.4, 22.2, 22.6,22.7, 26.17, 26.24, 27.1, 27.5, 44.2, 107.9, 108.8, 117.4, 117.8, 119.3,127.3, 128.0, 128.77, 128.83, 129.98, 130.01, 132.2, 134.2, 141.5,145.4, 150.1, 176.5; FABMS obsd 465.3074 [(M+H)⁺], calcd 465.3077(C₃₁H₃₇BN₂O); Anal. calcd for C₃₁H₃₇BN₂O: C, 80.17; H, 8.03; N, 6.03.Found: C, 79.98; H, 8.06; N, 5.95; λ_(abs) 393 nm.

10-(Dimethylboryl)-1-(4-methylbenzoyl)-5-phenyldipyrromethane (6a-BMe₂).A solution of 2a (0.340 g, 1.00 mmol) in CH₂Cl₂ (2 mL) was treated withTEA (0.335 mL, 2.40 mmol) followed by Me₂B—Br (0.390 mL, 1.00 mmol).After 30 min, the mixture was passed through a pad of silica (4×8 cm)eluting with CH₂Cl₂. The product eluted as a fast-moving yellow band,which upon concentration afforded an orange oil (0.344 g, 91%): ¹H NMR δ0.04 (s, 3H), 0.15 (s, 3H), 2.48 (s, 3H), 5.66 (s, 1H), 5.87–5.92 (m,1H), 6.15–6.19 (m, 1H), 6.43 (d, J=4.0 Hz, 1H), 6.70–6.75 (m, 1H),7.24–7.38 (m, 8H), 7.84–7.88 (br, 1H), 8.11 (d, J=8.0 Hz, 2H); ¹³C NMR δ6.8, 22.1, 44.1, 107.9, 108.6, 117.5, 118.3, 119.3, 127.3, 128.1, 128.8,128.9, 129.95, 129.99, 132.0, 133.1, 141.4, 145.5, 150.1, 176.1; FABMSobsd 381.2158 [(M+H)⁺], calcd 381.2138 (C₂₅H₂₅BN₂O); Anal. calcd forC₂₅H₂₅BN₂O: C, 78.96; H, 6.63; N, 7.37. Found: C, 78.66; H, 6.60; N,7.28; λ_(abs) 393 nm.

10-(9-Borabicyclo[3.3.1]non-9-yl)-1-(4-methylbenzoyl)-5-phenyldipyrromethane(6a-BBN). A solution of 2a (0.680 g, 2.00 mmol) in CH₂Cl₂ (4 mL) wastreated with TEA (0.670 mL, 4.80 mmol) followed by 9-BBN-OTf (8.00 mL,4.00 mmol, 0.5 M in hexanes). After 30 min, the mixture was passedthrough a pad of silica (4×8 cm) eluting with CH₂Cl₂. The product elutedas a fast-moving yellow band, which upon concentration afforded ayellow-orange solid (0.863 g, 94%): mp 187° C. (dec.); ¹H NMR δ0.66–0.71 (m, 2H), 1.65–1.84 (m, 6H), 1.95–2.25 (m, 6H), 2.48 (s, 3H),5.83–5.86 (m, 1H), 6.01 (s, 1H), 6.13–6.17 (m, 1H), 6.41 (d, J=4.0 Hz,1H), 6.69–6.73 (m, 1H), 7.18 (d, J=8.0 Hz, 2H), 7.22–7.38 (m, 6H),7.83–7.87 (br, 1H), 8.11 (d, J=8.0 Hz, 2H); ¹³C NMR δ 22.0, 23.8, 25.1,25.9, 26.4, 30.5, 30.8, 34.48, 34.54, 44.7, 108.1, 108.5, 117.4, 118.2,120.8, 127.0, 128.1, 128.4, 128.6, 129.7, 129.9, 132.3, 134.8, 142.1,145.0, 151.9, 174.4; ¹¹B NMR δ 12.34; FABMS obsd 460.2674 [M⁺], calcd460.2686 (C₃₁H₃₃BN₂O); Anal. calcd for C₃₁H₃₃BN₂O: C, 80.87; H, 7.22; N,6.08. Found: C, 78.96; H, 7.13; N, 5.85; λ_(abs) 381 nm.

10-(9-Borabicyclo[3.3.1]non-9-yl)-1-(4-methylbenzoyl)dipyrromethane(6b-BBN). Following the procedure for 6a-BBN, reaction of 2b (0.529 g,2.00 mmol) afforded a yellow-orange solid (0.696 g, 91%): mp 147° C.(dec.); ¹H NMR δ 0.71–0.78 (m, 2H), 1.67–1.75 (m, 4H), 1.76–1.91 (m,4H), 1.98–2.14 (m, 2H) 2.16–2.26 (m, 2H), 2.48 (s, 3H), 4.34 (s, 2H),6.03–6.06 (m, 1H), 6.16–6.18 (m, 1H), 6.36 (d, J=4.0 Hz, 1H), 6.69–6.72(m, 1H), 7.29 (d, J=4.0 Hz, 1H), 7.36 (d, J=8.0 Hz, 2H), 7.90–7.94 (br,1H), 8.11 (d, J=8.0 Hz, 2H); ¹³C NMR δ 22.1, 24.0, 25.2, 26.8, 29.5,31.5, 34.5, 107.1, 108.7, 117.5, 118.3, 120.7, 128.2, 128.7, 129.8,129.9, 135.3, 145.0, 149.5, 174.1; ¹¹B NMR δ 12.74; FABMS obsd 384.2395[M⁺], calcd 384.2373 (C₂₅H₂₉BN₂O); Anal. calcd for C₂₅H₂₉BN₂O: C, 78.13;H, 7.61; N, 7.29. Found: C, 78.17; H, 7.58; N, 7.09; λ_(abs) 380 nm.

10-(9-Borabicyclo[3.3.1]non-9-yl)-1-hexanoyl-5-pentyldipyrromethane(6c-BBN). Following the procedure for 6a-BBN, reaction of 2c (0.529 g,2.00 mmol) afforded an orange oil (0.758 g, 87%): ¹H NMR δ 0.55–0.64 (m,2H), 0.82–0.94 (m, 6H), 1.19–1.54 (m, 12H), 1.62–1.91 (m, 8H), 1.96–2.17(m, 6H), 2.81 (t, J=8.0 Hz, 2H), 4.43 (t, J=8.0 Hz, 1H), 6.03–6.06 (m,1H), 6.13–6.17 (m, 1H), 6.39 (d, J=4.0 Hz, 1H), 6.62–6.67 (m, 1H), 7.05(d, J=4.0 Hz, 1H), 7.76–7.80 (br, 1H); ¹³C NMR δ 14.1, 14.2, 22.5, 22.6,22.7, 24.0, 25.0, 25.8, 26.3, 27.6, 30.7, 30.8, 31.5, 31.7, 32.2, 34.19,32.22, 36.4, 39.2, 105.2, 108.5, 117.0, 117.57, 117.63, 133.5, 136.5,154.8, 184.3; ¹¹B NMR δ 13.22; FABMS obsd 434.3481 [M⁺], calcd 434.3468(C₂₈H₄₃BN₂O); Anal. calcd for C₂₈H₄₃BN₂O: C, 77.41; H, 9.98; N, 6.45.Found: C, 75.22; H, 9.90; N, 6.40; λ_(abs) 345 nm.

10-(9-Borabicyclo[3.3.1]non-9-yl)-1-(4-methoxybenzoyl)-5-(4-methoxyphenyl)dipyrromethane(6d-BBN). Following the procedure for 6a-BBN, reaction of 2d (0.773 g,2.00 mmol) afforded a yellow-brown solid (0.986 g, 97%): mp 72–73° C.;¹H NMR δ 0.64–0.74 (m, 2H), 1.62–1.86 (m, 6H), 1.98–2.24 (m, 6H), 3.79(s, 3H), 3.92 (s, 3H), 5.82–5.87 (m, 1H), 5.96 (s, 1H), 6.12–6.17 (m, 1H), 6.40 (d, J=4.0 Hz, 1H), 6.69–6.72 (m, 1H), 6.84 (d, J=8.0 Hz, 2H),7.05 (d, J=8.0 Hz, 2H), 7.10 (d, J=8.0 Hz, 2H), 7.30 (d, J=4.0 Hz, 1H),7.84–7.88 (br, 1H), 8.21 (d, J=8.0 Hz, 2H); ¹³C NMR δ 24.0, 25.2, 26.0,26.5, 30.6, 30.9, 34.6, 34.7, 44.0, 55.4, 55.8, 107.9, 108.6, 114.0,114.7, 117.4, 117.8, 120.5, 123.5, 129.6, 130.0, 133.0, 134.4, 134.5,151.7, 158.6, 164.4, 173.8; ¹¹B NMR δ 12.69; FABMS obsd 506.2749 [M⁺],calcd 506.2741 (C₃₂H₃₅BN₂O₃); Anal. calcd for C₃₂H₃₅BN₂O₃: C, 75.89; H,6.97; N, 5.53. Found: C, 74.75; H, 7.37; N, 5.01; λ_(abs) 388 nm.

10-(Dibutylboryl)-1-(pentafluorobenzoyl)-5-pentafluorophenyldipyrromethane(6e-BBu₂). Following the procedure for 6a-BBu₂, reaction of 2e (0.506 g,1.00 mmol) afforded an orange oil (0.608 g, 97%): ¹H NMR δ 0.13–0.35 (m,2H), 0.58–1.39 (m, 16H), 5.94 (s, 1H), 6.00 (s, 1H), 6.15–6.20 (m, 1H),6.61 (d, J=4.0 Hz, 1H), 6.74–6.80 (m, 1H), 7.04–7.10 (m, 1H), 8.05–8.09(br, 1H); ¹³C NMR δ 14.1, 14.3, 20.9, 21.4, 26.0, 26.2, 26.9, 27.4,33.5, 33.9, 108.5, 109.2, 109.4, 111.3, 118.8, 119.6, 119.7, 119.8,122.1, 122.3, 127.0, 136.9 (m), 138.0, 139.6 (m), 142.1 (m), 142.9 (m),143.9 (m), 144.4 (m), 145.5 (m), 146.4 (m), 147.0 (m), 150.6, 166.0.This compound partially decomplexed to 2e upon handling due to exposureto moisture.

10-(Dibutylboryl)-1-(4-iodobenzoyl)-5-mesityldipyrromethane (6f-BBu₂).Following the procedure for 6a-BBu₂, reaction of 2f (0.494 g, 1.00 mmol)afforded a yellow-orange solid (0.548 g, 89%): mp 53–54° C.; ¹H NMR δ−0.25–−0.17 (m, 1H), 0.24–0.39 (m, 2H), 0.55–0.98 (m, 13H), 1.14–1.27(m, 2H), 2.15 (s, 6H), 2.62 (s, 3H), 5.88 (s, 1H), 5.90–5.93 (m, 1H),6.16–6.20 (m, 1H), 6.50 (d, J=4.0 Hz, 1H), 6.66–6.70 (m, 1H), 6.83 (s,2H), 7.17 (d, J=4.0 Hz, 1H), 7.80–7.84 (br, 1H), 7.85–7.94 (m, 4H); ¹³CNMR δ 14.3, 14.5, 20.9, 21.2, 21.8, 26.1, 26.2, 27.3, 27.5, 40.1, 101.9,108.0, 108.9, 116.8, 117.0, 122.8, 130.0, 130.1, 130.6, 130.9, 134.8,135.3, 136.9, 137.2, 138.6, 153.0, 174.7; FABMS obsd 619.2390 [(M+H)⁺],calcd 619.2357 (C₃₃H₄₀BIN₂O); Anal. calcd for C₃₃H₄OBIN₂O: C, 64.09; H,6.52; N, 4.53. Found: C, 64.08; H, 6.62; N, 4.40; λ_(abs) 404 nm.

10-(9-Borabicyclo[3.3.1]non-9-yl)-1-(4-bromophenyl)-5-[4-(2-trimethylsilyl)ethynylphenyl]dipyrromethane(6g-BBN). Following the procedure for 6a-BBN, reaction of 2g (0.529 g,2.00 mmol) afforded a yellow-orange solid (1.19 g, 96%): mp 172° C.(dec.); ¹H NMR δ 0.24 (s, 9H), 0.64–0.73 (m, 2H), 1.64–1.85 (m, 6H),1.94–2.09 (m, 4H), 2.12–2.24 (m, 2H), 5.83 (s, 1H), 6.00 (s, 1H),6.13–6.18 (m, 1H), 6.39 (d, J=4.0 Hz, 1H), 6.71–6.75 (m, 1H), 7.09 (d,J=8.0 Hz, 2H), 7.32 (d, J=4.0 Hz, 1H), 7.40 (d, J=8.0 Hz, 2H), 7.68–7.74(m, 2H), 7.82–7.86 (br, 1H) 8.02–8.10 (m, 2H); ¹³C NMR δ 0.18, 23.8,25.1, 25.9, 26.6, 30.7, 30.8, 34.6, 44.8, 94.7, 104.9, 108.4, 108.8,117.9, 118.7, 121.6, 122.1, 128.4, 129.2, 129.7, 131.0, 131.7, 132.4,132.6, 132.7, 135.1, 142.4, 152.5, 173.2; ¹¹B NMR δ 13.98; FABMS obsd620.2057 [M⁺], calcd 620.2030 (C₃₅H₃₈BBrN₂OSi); Anal. calcd forC₃₅H₃₈BBrN₂OSi: C, 67.64; H, 6.16; N, 4.51. Found: C, 67.41; H, 6.26; N,4.43; λ_(abs) 388 nm.

10-(9-Borabicyclo[3.3.1]non-9-yl)-1-(4-methylbenzoyl)-5-(pentafluorophenyl)dipyrromethane(6h-BBN). Following the procedure for 6a-BBN, reaction of 2h (0.430 g,1.00 mmol) afforded a yellow-orange solid (0.512 g, 93%): mp 154–156° C.(dec.); ¹H NMR δ 0.58–0.64 (m, 1H), 0.68–0.74 (m, 1H), 1.58–1.85 (m,6H), 1.94–2.24 (m, 6H), 2.50 (s, 3H), 5.79 (s, 1H), 6.12–6.18 (m, 1H),6.30 (s, 1H), 6.60 (d, J=4.0 Hz, 1H), 6.62–6.68 (m, 1H), 7.38 (d, J=4.0Hz, 1H), 7.39 (d, J=8.0 Hz, 2H), 7.75–7.78 (br, 1H), 8.15 (d, J=8.0 Hz,2H); ¹³C NMR δ 22.2, 23.9, 25.1, 26.3, 27.2, 29.8, 31.3, 34.67, 34.71,36.3, 106.9, 109.2, 117.4, 118.3, 120.56, 120.60, 120.64, 127.9, 129.6,130.07, 130.14, 135.9, 136.8 (m), 139.4 (m), 142.0 (m), 144.4 (m),145.8, 146.4, 146.9 (m), 175.9; FABMS obsd 550.2229 [M⁺], calcd 550.2215(C₃₁H₂₈BF₅N₂O); Anal. calcd for C₃₁H₂₈BF₅N₂O: C, 67.65; H, 5.13; N,5.09. Found: C, 68.05; H, 5.23; N, 4.92; λ_(abs) 377 nm.

10-(Dibutylboryl)-1-(4-methylbenzoyl)-5-(pentafluorophenyl)dipyrromethane(6h-BBu₂). Following the procedure for 6a-BBu₂, reaction of 2h (0.430 g,1.00 mmol) afforded an orange oil (0.497 g, 90%): ¹H NMR δ 0.16–0.35 (m,2H), 0.54–1.25 (m, 16H), 2.48 (s, 3H), 5.94–6.02 (m, 2H), 6.14–6.18 (m,1H), 6.57 (d, J=4.0 Hz, 1H), 6.72–6.78 (m, 1H), 7.24 (d, J=4.0 Hz, 1H),7.38 (d, J=8.0 Hz, 2H), 8.06–8.10 (br, 1H), 8.12 (d, J=8.0 Hz, 2H); ¹³CMNR δ 14.2, 14.4, 21.5, 21.8, 22.2, 26.1, 26.3, 27.1, 27.6, 33.7, 107.9,109.0, 117.4, 118.3, 119.68, 119.72, 119.76, 127.7, 128.0, 130.1, 130.2,135.0, 145.6, 146.1, 177.6; FABMS obsd 555.2627 [(M+H)⁺], calcd 555.2606(C₃₁H₃₂BF₅N₂O); Anal. calcd for C₃₁H₃₂BF₅N₂O: C, 67.16; H, 5.82; N,5.05. Found: C, 67.00; H, 5.78; N, 4.91; λ_(abs) 386 nm.

10-(Dibutylboryl)-1-(pentafluorobenzoyl)dipyrromethane (6i-BBu₂).Following the procedure for 6a-BBu₂, reaction of 2i (0.340 g, 1.00 mmol)afforded an orange oil (0.412 g, 89%): ¹H NMR δ 0.58–0.68 (m, 2H),0.74–0.92 (m, 10H), 1.00–1.08 (m, 2H), 1.16–1.30 (m, 4H), 4.09 (s, 2H),6.04–6.09 (m, 1H), 6.14–6.20 (m, 1H), 6.45 (d, J=4.0 Hz, 1H), 6.70–6.75(m, 1H), 7.01–7.06 (m, 1H), 7.90–7.93 (br, 1H); ¹³C NMR δ 14.4, 22.0,26.2, 27.3, 107.6, 109.1, 117.8, 120.21, 120.26, 120.30, 121.9, 126.9,137.5, 152.1, 164.1; FABMS obsd 465.2179 [(M+H)⁺], calcd 465.2137(C₂₄H₂₆BF₅N₂O); Anal. calcd for C₂₄H₂₅BF₅N₂O: C, 62.09; H, 5.64 ; N,6.03. Found: C, 61.31; H, 5.63; N, 5.93; λ_(abs) 382 nm.

Acylation-Boron Complexation Procedure, Exemplified for 6a-BBN. Asolution of EtMgBr (20.0 mL, 20.0 mmol, 1.0 M in THF) was added slowlyto a solution of 1a (2.22 g, 10.0 mmol) in THF (10 mL) under argon. Theresulting mixture was stirred at room temperature for 10 min, and thencooled to −78° C. A solution of S-2-pyridyl 4-methylbenzothioate (5a,2.29 g, 10.0 mmol) in THF (10 mL) was added. The solution was stirred at−78° C. for 10 min, then warmed to room temperature. The reactionmixture was quenched by addition of saturated aqueous NH₄Cl (40 mL). Themixture was extracted with ethyl acetate (30 mL). The organic layer waswashed (water and brine), dried (Na₂SO₄), and filtered. The filtrate wasconcentrated. The crude product (a red-orange oil) thus obtained wasdissolved in CH₂Cl₂ (20 mL) and treated with TEA (3.35 mL, 24.0 mmol)followed by 9-BBN-OTf (40 mL, 20.0 mmol, 0.5 M in hexane) with stirringat room temperature. A precipitate formed which largely consisted of thesalt of TEA and triflic acid. After 1 h, the mixture was poured onto apad of silica (4×8 cm) eluting with CH₂Cl₂. The product eluted as afast-moving yellow band, which upon concentration afforded ayellow-orange solid (3.12 g, 67%) with satisfactory characterizationdata (mp, ¹H NMR spectrum and FABMS) as reported above.

Note: The use of boron complexation to isolate the 1-acyldipyrromethaneenables use of stoichiometric quantities of reagents rather than excessas employed previously. Thus, the 1-acylation of dipyrromethanes wasconducted with slight modification to the standard procedure.Previously, 2.5 molar equiv of EtMgBr was used for the acylation ofdipyrromethane (1) with 1.0 molar equiv of a Mukaiyama reagent (5) inorder to avoid co-chromatography of the unreacted 5 and the product 2.²(The unreacted Mukaiyama reagent is consumed by EtMgBr, affording theketone³⁰). Given that the 1-acyldipyrromethane is to be isolated as aboron complex, complete consumption of the Mukaiyama reagent is notnecessary.

Scale-up Procedure. A solution of EtMgBr (80.0 mL, 80.0 mmol, 1.0 M inTHF) was added slowly to a solution of 1a (8.88 g, 40.0 mmol) in THF (40mL) under argon. The resulting mixture was stirred at room temperaturefor 10 min, and then cooled to −78° C. A solution of S-2-pyridyl4-methylbenzothioate (5a, 9.16 g, 40.0 mmol) in THF (40 mL) was added.The solution was stirred at −78° C. for 10 min, then warmed to roomtemperature. The reaction mixture was quenched by addition of saturatedaqueous NH₄Cl. The mixture was extracted with ethyl acetate. The organiclayer was dried (Na₂SO₄) and filtered. The filtrate was concentrated.The crude product (a red-orange oil) thus obtained was dissolved intoluene (80 mL) and treated with TEA (13.4 mL, 96.0 mmol) followed by9-BBN-OTf (160 mL, 80.0 mmol, 0.5 M in hexanes) with stirring at roomtemperature. A precipitate formed immediately, which largely consistedof the title compound and the salt of TEA and triflic acid. After 1 h,the mixture was filtered through a Buchner funnel using coarse filterpaper. The filtered material was washed with water, washed withmethanol, and then dried in vacuo to afford a yellow powder (9.63 g,52%). The filtrate was concentrated and passed through a silica padeluting with CH₂Cl₂/hexanes afforded 1.77 g of the title compound. Thecombined yield is 11.4 g (62%) and the characterization data aresatisfactory (mp, ¹H NMR, ¹³C NMR and FABMS spectra) as reported above.

10-(9-Borabicyclo[3.3.1]non-9-yl)-1-(4-methylbenzoyl)dipyrromethane(6b-BBN). Following the acylation-complexation procedure, reaction of 1b(1.46 g, 10.0 mmol) with EtMgBr (20.0 mL, 20.0 mmol, 1.0 M in THF)followed by treatment with 5a (2.29 g, 10.0 mmol) afforded crude 2b.Boron complexation with TEA (3.35 mL, 24.0 mmol) and 9-BBN-OTf (40.0 mL,20.0 mmol, 0.5 M in hexanes) in CH₂Cl₂ followed by passage through a padof silica [CH₂Cl₂/hexanes (1:1)] afforded a solid which upon triturationwith hexanes afforded yellow crystals (2.30 g, 60%) with satisfactorycharacterization data (mp, ¹H NMR, and elemental analysis) as reportedabove.

10-(9-Borabicyclo[3.3.1]non-9-yl)-1′-hexanoyl-5-pentyldipyrromethane(6c-BBN). Following the acylation-complexation procedure, reaction of 1c(2.16 g, 10.0 mmol) with EtMgBr (20.0 mL, 20.0 mmol, 1.0 M in THF)followed by treatment with 5f (2.09 g, 10.0 mmol) afforded crude 2c.Boron complexation with TEA (3.35 ml, 24.0 mmol) and 9-BBN-OTf (40.0 mL,20.0 mmol, 0.5 M in hexanes) in CH₂Cl₂ followed by passage through a padof silica [CH₂Cl₂/hexanes (1:1)] afforded an orange oil (2.59 g, 60%)with satisfactory characterization data (¹H NMR and ¹³C NMR spectra andFABMS) as reported above.

10-(9-Borabicyclo[3.3.1]non-9-yl)-1-(4-methoxybenzoyl)-5-(4-methoxyphenyl)dipyrromethane (6d-BBN). Following the acylation-complexation procedure,reaction of 1d (2.45 g, 10.0 mmol) with EtMgBr (20.0 mL, 20.0 mmol, 1.0M in THF) followed by treatment with 5b (2.45 g, 10.0 mmol) affordedcrude 2d. Boron complexation with TEA (3.35 mL, 24.0 mmol) and 9-BBN-OTf(40.0 mL, 20.0 mmol, 0.5 M in hexanes) in CH₂Cl₂ afforded ayellow-orange precipitate. The precipitate was filtered and dissolved in50 mL of CH₂Cl₂. The solution was washed with water and brine, dried(Na₂SO₄), and concentrated to dryness. The resulting yellow solid wasstirred in Et₂O for 1 min, filtered, washed with Et₂O and hexanes,dissolved in 20 mL of CH₂Cl₂ and concentrated to dryness, affordingyellow crystals (2.81 g, 56%). The filtrates (from reaction mixture andstirring in Et₂O) were combined, concentrated, and filtered through apad of silica CH₂Cl₂/hexanes (1:1), affording additional product (0.52g). The total yield is 3.33 g (66%) and the characterization data aresatisfactory (mp, ¹H NMR, and elemental analysis) as reported above.

10-(Dibutylboryl)-1-(4-iodobenzoyl)-5-mesityldipyrromethane (6f-BBu₂).

Following the acylation-complexation procedure, reaction of 1f (2.64 g,10.0 mmol) with EtMgBr (20.0 mL, 20.0 mmol, 1.0 M in THF) followed bytreatment with 5d (2.29 g, 10.0 mmol) afforded crude 2f. Boroncomplexation with TEA (3.35 mL, 24.0 mmol) and dibutylboron triflate(20.0 mL, 20.0 mmol, 1.0 M in CH₂Cl₂) in CH₂Cl₂ followed by passagethrough a pad of silica [CH₂Cl₂/hexanes (1:2)] afforded a golden-yellowamorphous powder (4.23 g, 68%) with satisfactory characterization data(mp, ¹H NMR, and elemental analysis) as reported above.

10-(9-Borabicyclo[3.3.1]non-9-yl)-1-(4-bromobenzoyl)-5-[4-(trimethylsilylethynyl)phenyl]dipyrromethane(6g-BBN). Following the acylation-complexation procedure, reaction of 1g(3.18 g, 10.0 mmol) with EtMgBr (20.0 mL, 20.0 mmol, 1.0 M in THF)followed by treatment with 5e (2.93 g, 10.0 mmol) afforded crude 2g.Boron complexation with TEA (3.35 mL, 24.0 mmol) and 9-BBN-OTf (40.0 mL,20.0 mmol, 0.5 M in hexanes) in CH₂Cl₂ followed by passage through a padof silica [CH₂Cl₂/hexanes (1:1)] afforded orange-yellow crystals (4.38g, 71%) with satisfactory characterization data (mp, ¹H NMR, andelemental analysis) as reported above.

10-(9-Borabicyclo[3.3.1]non-9-yl)-1-(4-methylbenzoyl)-5-(pentafluorophenyl)dipyrromethane(6h-BBN). Following the acylation-complexation procedure, reaction of 1h (3.12 g, 10.0 mmol) with EtMgBr (20.0 mL, 20.0 mmol, 1.0 M in THF)followed by treatment with 5a (2.29 g, 10.0 mmol) afforded crude 2h.Boron complexation with TEA (3.35 mL, 24.0 mmol) and 9-BBN-OTf (40.0 mL,20.0 mmol, 0.5 M in hexanes) in CH₂Cl₂ followed by passage through a padof silica [CH₂Cl₂/hexanes (1:1)] afforded yellow crystals (3.17 g, 58%)with satisfactory characterization data (mp, ¹H NMR, and elementalanalysis) as reported above.

Decomplexation Procedure, Exemplified for 6a-BBN→2a. A solution of6a-BBN (0.230 g, 0.500 mmol) in THF (0.8 mL) was treated with 1-pentanol(0.2 mL). The reaction mixture was heated at reflux. After 1 h, TLC(silica/CH₂Cl₂) examination showed almost complete consumption of boroncomplex 6a-BBN. The mixture was concentrated to dryness and theresulting oily residue was treated with 5 mL of hexanes. The oilsolidified upon standing for 5 min. The mixture was heated gently underreflux for 5 min (the solid dissolved completely). The mixture wascooled, affording a precipitate upon standing for a few hours. Thesolvent was decanted. The solid was dissolved in a minimal amount ofCH₂Cl₂ (˜0.2 mL), and the title compound was precipitated upon additionof hexanes. The precipitate was collected and dried in vacuo to afford adark-yellow powder (0.118 g, 66%). The hexanes solution was concentratedto half of the starting volume. The resulting precipitate was filtered,dissolved in a minimal volume of CH₂Cl₂ and precipitated upon additionof hexanes, affording an additional 0.030 g of title compound. Thecombined yield (0.148 g) is 83%: mp 64–65° C. (lit.² 70–72° C.); ¹H NMR(CDCl₃) δ 2.42 (s, 3H), 5.54 (s, 1H), 5.99 (s, 1H), 6.04–6.08 (m, 1H),6.16–6.20 (m, 1H), 6.72 (s, 1 H), 6.79–6.83 (m, 1H), 7.36–7.22 (m, 8H),7.75 (d, J=8.0 Hz, 2H), 7.97–8.00 (br, 1H) 9.34–9.37 (br, 1H); FABMSobsd 340.1593 [M⁺], calcd 340.1576 (C₂₃H₂₀N₂O).

Notes: High ratios of 1-pentanol/THF can be used and result in fasterreaction (20 min), but can cause interference upon crystallization. Inmost cases, it is important to remove I-pentanol completely because ofthe high solubility of 1-acyldipyrromethanes in 1-pentanol.

1-(4-Methylbenzoyl)dipyrromethane (2b). Following the decomplexationprocedure, a sample of 6b-BBN (0.74 g, 2.0 mmol) was dissolved in THF (3mL) and I-pentanol (1 mL) was added. The mixture was refluxed for 1 h,then concentrated and treated with 5 mL of hexanes. The resultingprecipitate was filtered, washed with hexanes and dried under vacuo togive pale yellow crystals (0.43 g, 81%) with satisfactorycharacterization data (mp, ¹H NMR, and elemental analysis) as describedabove.

1-Hexanoyl-5-pentyldipyrromethane (2c). Following the decomplexationprocedure, reaction of 6c-BBN (0.869 g, 2.00 mmol) with 1-pentanol (1.00mL, 10.0 mmol) in THF at reflux afforded a crude product. The crudeproduct was passed through a pad of alumina [CH₂Cl₂→CH₂Cl₂/ethyl acetate(4:1)] affording a light yellow oil (0.514 g, 82%) with satisfactorycharacterization data (¹H NMR, elemental analysis) as described above.

1-(4-Methoxybenzoyl)-5-(4-methoxyphenyl)dipyrromethane (2d). Followingthe decomplexation procedure, a suspension of 6d-BBN (1.01 g, 2.00 mmol)in THF (3.2 mL) and 1-pentanol (0.8 mL) was refluxed for 1.5 h. Themixture was concentrated and the residue was dissolved in a small volumeof CH₂Cl₂ and treated with hexanes. An oily precipitate was formed. Thesolvent was decanted. The residue was dried under vacuum, washedthoroughly with hexanes and dried again to afford a pale brown amorphouspowder (0.610 g, 78%): mp 58–61° C. (dec.) (lit.⁷ 113–114° C.). The ¹HNMR data and elemental analysis data were consistent with those for thesame compound obtained by a different route.⁷

1-(4-Iodobenzoyl)-5-mesityldipyrromethane (2f). A sample of 6f-BBu₂(1.24 g, 2.00 mmol) was dissolved in 1-pentanol (4.0 mL). The solutionwas heated at 70–80° C. After 1 h the mixture was concentrated and 20 mLof hexanes was added. The mixture was heated at reflux for 2 min, andthen cooled to room temperature. After standing overnight at −15° C.,the precipitate was collected, dissolved in a minimum volume of CH₂Cl₂,and precipitated with hexanes. The precipitate was collected and driedin vacuo to afford a dark powder (0.639 g, 65%): mp 166–170° C. (lit.²163° C.). The ¹H NMR and elemental analysis data were consistent withthose for the same compound obtained by a different route.²

5,10-Bis(4-methylphenyl)-15,20-diphenylporphyrin (8) from 6a-BBu₂. Asample of 1-acyldipyrromethane-boron complex 6a-BBu₂ (0.116 g, 0.250mmol) was dissolved in dry THF/methanol (3:1, 6 mL) at room temperaturein a round-bottomed flask fitted with a vented rubber septum and floodedwith argon. The septum was removed as needed to add NaBH₄ (0.238 g, 6.25mmol, 25 mol equiv) in small portions with rapid stirring. The progressof the reduction was monitored by TLC analysis [alumina, CH₂Cl₂/ethylacetate (3:2)] of reaction aliquots. After the reaction was complete(about 40 min), the reaction mixture was poured into a stirred mixtureof saturated aqueous NH₄C₁ and CH₂Cl₂. The organic phase was separated,washed with water, dried (Na₂SO₄), and concentrated under reducedpressure to yield the monocarbinol as a foamlike solid. To the flaskcontaining the dipyrromethane-moncarbinol (0.250 mmol assumingquantitative reduction) was added reagent-grade CH₂Cl₂ (50 mL). Themixture was stirred for 5 min to achieve dissolution, and then Yb(OTf)₃(0.010 g, 0.016 mmol, 0.32 mM) was added. The reaction was monitored byabsorption spectroscopy [by injecting a 50 μL reaction aliquot into asolution of DDQ (300 μL, 0.01 M in toluene); then 50 μL of the resultingoxidized mixture was dissolved in CH₂Cl₂/EtOH (3:1, 3 mL), and theabsorption spectrum was recorded]. After acid-catalyzed condensation for60 min, DDQ (0.085 mg, 0.375 mmol) was added. The mixture was stirred atroom temperature for 1 h. TEA was added and the entire reaction mixturewas passed through a pad of silica and eluted with CH₂Cl₂ until theeluant was no longer purple. The resulting porphyrin-containing solutionwas concentrated by rotary evaporation to give a purple solid. The solidwas triturated with methanol and dried in vacuo affording a crystallinepurple solid (0.021 g, 26%). The characterization data (¹H NMR, LDMS,and UV-vis spectra) were consistent with the reported values.²

5,10-Bis(4-methylphenyl)-15,20-diphenylporphyrin (8) from 6a-BBN.Following the porphyrin formation procedure for 8 from 6a-BBu₂, reactionof 6a-BBN (0.460 g, 1.00 mmol) afforded a purple solid (0.054 g, 17%)with satisfactory characterization data (¹H NMR, LDMS, and UV-visspectra).

10-(9-Borabicyclo[3.3.1]non-9-yl)-5-phenyl-1,9-di-p-toluoyldipyrromethane(3a-BBN). A suspension of 6a-BBN (460 mg, 1.0 mmol) in THF (1 mL) and1,1,1,3,3,3-hexamethyldisilazane (208 μL, 1.0 mmol) was treated withEtMgBr (2.20 mL, 2.20 mmol, 1 M solution in THF). The mixture wasstirred at room temperature for 10 min. Then a solution of S-2-pyridyl4-methylbenzothioate (5a, 274 mg, 1.2 mmol, 1 M solution in THF) wasadded. The mixture was stirred at room temperature for 0.5 h, and thenthe mixture was quenched by addition of a half-saturated aqueoussolution of NH₄Cl (10 mL). Et₂O (10 mL) was added. The organic layer waswashed with a saturated aqueous solution of NaHCO₃ (5 mL) followed bybrine (10 mL). The organic layer was dried (Na₂SO₄) and concentrated todryness under vacuum. The resulting brown residue (expected yield fromcrude NMR was 86%) was treated with small amount of Et₂O (˜1–2 mL),affording a suspension consisting of a brown solution and a brightyellow powder. A small amount of n-hexanes was added (˜2–4 mL). Theresulting mixture was filtered on a Buchner funnel. The precipitate thusobtained was washed with cold methanol (2 mL) to afford a yellow powder(392 mg, 68%): ¹H NMR δ 0.70–0.73 (m, 2H), 1.68–2.20 (m, 12H), 2.41 (s,3H), 2.48 (s, 3H), 6.00–6.02 (m, 1H), 6.10 (s, 1H), 6.46 (d, J=4.5 Hz,1H), 6.80–6.82 (m, 1H), 7.17–7.38 (m, 10H), 7.77 (d, J=8.4 Hz, 2H), 8.13(d, J=8.1 Hz, 2H), 9.15 (brs, 1H); ¹³C NMR δ 21.8, 22.2, 23.9, 25.2,26.2, 26.3, 30.7, 31.0, 34.5, 34.6, 45.0, 111.3, 118.5, 119.9, 120.7,127.6, 128.1, 128.5, 129.0, 129.1, 129.2, 129.9, 130.0, 131.0, 135.2,135.8, 140.4, 141.0, 142.5, 145.4, 150.0, 175.2, 184.3. Anal. calcd forC₃₉H₃₉BN₂O₂: C, 80.96; H, 6.79; N, 4.84. Found: C, 81.19; H, 6.96; N,4.65.

Scale-up Procedure.10-(9-Borabicyclo[3.3.1]non-9-yl)-5-phenyl-1,9-di-p-toluoyldipyrromethane(3a-BBN). A suspension of 6a-BBN (2.30 g, 5.0 mmol) in THF (5 mL) andHMDS (1.04 mL, 5.0 mmol) was treated with EtMgBr (10.0 mL, 10.0 mmol, 1M solution in THF). The mixture was stirred at room temperature for 15min. Then a solution of S-2-pyridyl 4-methylbenzothioate (5a, 1.26 g,1.1 mmol, 1 M solution in THF) was added. The mixture was stirred atroom temperature for 0.5 h. The mixture was quenched by addition of ahalf-saturated aqueous solution of NH₄Cl (50 mL). Et₂O (50 mL) wasadded. The organic layer was washed with aqueous NaHCO₃ (50 mL), water(50 mL) and brine (50 mL). The organic layer was dried (Na₂SO₄) andconcentrated to dryness under vacuum. The resulting brown residue wastreated with small amount of Et₂O (˜5–10 mL), affording a suspensionconsisting of a brown solution and a bright yellow powder. A smallamount of n-hexane was added (˜10 mL). The resulting mixture wasfiltered on a Buchner funnel. The precipitate thus obtained was furtherwashed with a small amount of n-hexanes (˜10–20 mL) to afford a yellowpowder (1.99 g, 69%): ¹H NMR δ 0.68–0.74 (m, 2H), 1.66–2.28 (m, 12H),2.42 (s, 3H), 2.48 (s, 3H), 6.00–6.02 (m, 1H), 6.11 (s, 1H), 6.46 (d,J=4.4 Hz, 1H), 6.81 (dd, J=4.0 Hz, J=2.4 Hz, 1H), 7.18 (d, J=8.0 Hz,2H), 7.25–7.38 (m, 8H), 7.77 (d, J=8.4 Hz, 2H), 8.13 (d, J=8.1 Hz, 2H),9.18 (brs, 1H); ¹³C NMR δ 21.8, 22.2, 23.9, 25.2, 26.2, 26.3, 30.8,31.0, 34.6, 34.7, 45.1, 127.6, 128.2, 128.5, 129.1, 129.2, 129.3, 130.0,130.1, 131.2, 135.3, 135.9, 140.5, 141.0, 142.5, 145.4, 150.1, 175.2,184.3; FABMS obsd 579.3176 [(M+H)⁺], calcd 579.3183 (C₃₉H₃₉BN₂O₂); Anal.calcd for C₃₉H₃₉BN₂O₂: C, 80.96; H, 6.79; N, 4.84 . Found: C, 80.54; H,6.70; N, 4.83.

An additional quantity of product was isolated from the filtrate as atin complex as follows. The filtrate was concentrated to dryness. Theresulting brown oily residue (˜830 mg) was dissolved in THF (2.4 mL) andtreated with n-pentanol (0.6 mL). The reaction was heated at reflux.After 1 h, TLC (silica, CH₂Cl₂) examination showed complete consumptionof the boron complex. The mixture was concentrated to dryness and theresulting dark brown oily residue was treated with TEA (0.42 mL, 3.0mmol) and Bu₂SnCl₂ (0.30 g, 1.0 mmol) in CH₂Cl₂ (10 mL) at roomtemperature for 30 min. The mixture was passed through a silica pad(CH₂Cl₂). The eluant was concentrated to dryness. The residue wasdissolved in a minimum amount of Et₂O. Then methanol was added, yieldinga precipitate, which upon filtration afforded thedibutyl[5,10-dihydro-5-phenyl-1,9-di-p-toluoyldipyrrinato]tin(IV)complex as a pale yellow solid (190 mg, 6%).

Decomplexation of10-(9-Borabicyclo[3.3.1]non-9-yl)-5-phenyl-1,9-di-p-toluoyldipyrromethane(3a-BBN→3a). A solution of 3a-BBN (0.289 g, 0.50 mmol) was in of THF(0.8 mL), was treated n-pentanol (0.2 mL). The reaction mixture washeated at reflux. After 1 h, TLC [silica, ethyl acetate/hexanes (4:1)]examination showed almost complete consumption of boron complex 3a-BBN.The mixture was concentrated to dryness and the resulting oily residuewas treated with 5 mL of hexanes to afford a light pink solid residue.The mixture was heated gently under reflux for 5 min (the soliddissolved completely). The mixture was cooled affording a precipitateupon standing for few minutes. The solvent was decanted. The solid wasdissolved in minimal amount of CH₂Cl₂ (˜0.2 mL), and the title compoundwas precipitated upon addition of hexanes. The resulting mixture wasfiltered on a Buchner funnel. The precipitate was collected and dried invacuo to afford a light pink powder (75 mg, 33%). The hexanes solutionswas concentrated to one fourth of the starting volume, to this minimalamount of CH₂Cl₂ (˜0.2 mL) and filtrate of the first precipitation wasadded, resulting a second batch of precipitate (130 mg, 57%). Thecombined yield (206 mg) is 90%: ¹H NMR δ 2.38 (s, 3H), 5.65 (s, 1H),5.97–5.98 (m, 2H), 6.58–6.59 (m, 2H), 7.20 (d, J=8.0 Hz, 4H), 7.31–7.33(m, 1H), 7.34–7.42 (m, 2H), 7.48–7.50 (m, 2H), 7.70 (d, J=8.0 Hz, 4H),11.04 (brs, 2H); FABMS obsd 458.1994 [(M+H)⁺], calcd 458.1969(C₃₁H₂₆N₂O₂).

5,15-Bis(4-methylphenyl)-10,20-diphenylporphyrin (8) from 3a-BBN. Asample of 3a-BBN (145 mg, 0.250 mmol) was dissolved in dry THF/methanol(3:1, 6 mL) at room temperature in a round-bottomed flask fitted with avented rubber septum and flooded with argon. The septum was removed asneeded to add NaBH₄ (946 mg, 25 mmol, 50 mol equiv) in small portionswith rapid stirring. The progress of the reduction was monitored by TLCanalysis [alumina, CH₂Cl₂/ethyl acetate (3:2)] of reaction aliquots.After the reaction was complete (about 40 min), the reaction mixture waspoured into a stirred mixture of saturated aqueous NH₄C₁ and CH₂Cl₂. Theorganic phase was separated, washed with water, dried (Na₂SO₄), andconcentrated under reduced pressure to yield the dicarbinol as afoamlike solid. To the flask containing the dipyrromethane-dicarbinol(0.250 mmol assuming quantitative reduction) was added reagent gradeCH₂Cl₂ (100 mL) and 1a (55 mg, 0.250 mmol). The mixture was stirred for5 min to achieve dissolution, and then Yb(OTf)₃ (206 mg, 0.325 mmol) wasadded. The reaction was monitored by absorption spectroscopy [Reactionmonitoring was performed by injecting a 25 μL reaction aliquot into asolution of DDQ (300 μL, 0.01 M in toluene); then 25 μL of the resultingoxidized mixture was dissolved in CH₂Cl₂/EtOH (3:1, 3 mL), and theabsorption spectrum was recorded.] Then [elapsed time of 15 min afterthe addition of Yb(OTf)₃)] DDQ (80 mg, 0.375 mmol) was added, and themixture was stirred at room temperature for 1 h. Then TEA was added, andthe entire reaction mixture was passed through a pad of alumina (toremove quinone species) and eluted with CH₂Cl₂ until the eluant was nolonger purple. The resulting porphyrin-containing solution wasconcentrated to give a purple solid. The solid was triturated withmethanol and dried in vacuo, affording a purple crystalline solid (32mg, 20%). The characterization data (¹H NMR, LDMS, and UV-vis spectra)were consistent with the reported values.⁷

10-(9-Borabicyclo[3.3.1]non-yl)-1-bromo-5-phenyl-9-p-toluoyldipyrromethane(9a-BBN). Following a similar procedure reported for the bromination of1-acyldipyrromethanes,⁴ a solution of 6a-BBN (464 mg, 1.00 mmol) in 10mL of dry THF was cooled to −78° C. under Ar. NBS (178 mg, 1.00 mmol)was added and the reaction mixture was stirred for 1 h at −78° C.Hexanes (10 mL) and water (10 mL) were added and the mixture was allowedto warm to room temperature. The organic phase was extracted withhexanes, dried (Na₂SO₄) and concentrated under reduced pressure withoutheating. Column chromatography [silica, hexanes/CH₂Cl₂ (1:1)] afforded ayellow orange powder (505 mg, 94%): mp 53° C. (dec.); ¹H NMR δ 0.64–0.72(m, 2H), 1.64–1.88 (m, 6H), 1.94–2.24 (m, 6H), 2.48 (s, 3H), 5.74–5.78(m, 1H), 5,96 (s, 1H), 6.05–6.09 (m, 1H), 6.41 (d, J=4.0 Hz, 1H), 7.18(d, J=8.0 Hz, 2H), 7.24–7.41 (m, 6H), 7.74 (brs, 1H), 8.12 (d, J=8.0 Hz,2H); ¹³C NMR δ 22.2, 22.9, 23.9, 25.2, 26.1, 26.4, 30.7, 30.9, 31.8,34.57, 34.64, 44.9, 97.4, 110.2, 110.8, 118.3, 120.7, 127.4, 128.2,128.5, 128.9, 129.9, 130.0, 133.9, 135.1, 141.6, 145.3, 151.0, 174.9;Anal. Calcd for C₃₁H₃₂BBrN₂O: C, 69.04; H, 5.98; N, 5.19. Found: C,70.30; H, 6.38; N, 4.86.

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The foregoing is illustrative of the present invention, and is not to beconstrued as limiting thereof. The invention is defined by the followingclaims, with equivalents of the claims to be included therein.

1. A 1-monoacyldipyrromethane-boron complex of the formula DMR¹R²,wherein: D is a 1-monoacyldipyrromethane, M is boron, and R¹ and R² areeach independently selected from the group consisting of alkyl, alkenyl,alkynyl, and aryl, each of which can be unsubstituted or substituted oneor more times with a substituent selected from the group consisting ofalkyl, alkenyl, alkynyl, aryl, alkoxy, alkylcarbonyl, alkylcarbonyloxy,alkylsulfinyl, alkylsulfonyl, alkylthio, halo, cyano, nitro, sulfo, oxo,formyl, azido, and carbamoyl.
 2. The 1-monoacyldipyrromethane-boroncomplex of claim 1 in solid form.
 3. The 1-monoacyldipyrromethane-boroncomplex of claim 1 in crystal solid form.